Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

2021 ◽  
Author(s):  
Byungji Kim ◽  
Qinglin Yang ◽  
Leslie W. Chan ◽  
Sangeeta N. Bhatia ◽  
Erkki Ruoslahti ◽  
...  
Keyword(s):  
Porous Silicon ◽  
Broad Spectrum ◽  
Therapeutic Efficacy ◽  
Bacterial Infections ◽  
Silicon Nanoparticles ◽  
First Line ◽  
Gram Positive ◽  
Gram Negative ◽  
Porous Silicon Nanoparticles

RNAi-mediated immunotherapy provided by fusogenic porous silicon nanoparticles demonstrates superior therapeutic efficacy against both Gram-positive and Gram-negative bacterial infections compared with first-line antibiotics.

scholarly journals Designer broad-spectrum polyimidazolium antibiotics

2020 ◽  
Vol 117 (49) ◽  
pp. 31376-31385
Author(s):  
Wenbin Zhong ◽  
Zhenyu Shi ◽  
Surendra H. Mahadevegowda ◽  
Bo Liu ◽  
Kaixi Zhang ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Electrostatic Interactions ◽  
Bacterial Infections ◽  
Cell Membranes ◽  
Intraperitoneal Administration ◽  
New Drugs ◽  
Gram Positive ◽  
Gram Negative ◽  
Show Evidence ◽  
A Site

For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positiveStaphylococcus aureuswe obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogenPseudomonas aeruginosa,PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.

scholarly journals Bacteriological profile and antibiogram of cancer patients admitted in intensive care unit of a tertiary care cancer hospital in central Kerala

2020 ◽  
Vol 8 (12) ◽  
pp. 4450
Author(s):  
Sanjana Ramakrishnan ◽  
Sourabh Radhakrishnan ◽  
Sonu Lazar Cyriac
Keyword(s):  
Cancer Patients ◽  
Bacterial Infections ◽  
Tertiary Care ◽  
Gram Positive ◽  
Cross Sectional ◽  
Gram Negative ◽  
Mortality And Morbidity ◽  
E Coli ◽  
Resistance To Penicillin ◽  
Study Laboratory

Background: Opportunistic bacterial infections remain a serious morbidity among cancer patients. This study was aimed to determine the bacteriological and antibiotic profile of cancer patients admitted to the ICU of a tertiary care centre.Methods: Cross sectional study was done among cancer patients admitted in the Oncology neutropenic ICU during the period from August 2017 to July 2019. All patients admitted with a proven diagnosis of cancer for whom at least one bacterial culture was sent from any site were included in the study. Laboratory on culture reports were obtained from patient files and analysed.Results: A total of 278 samples from 256 patients (60±11.6 years) were analysed. Among the 111/278 positive cultures, 29 were blood samples and 1 was a pleural fluid sample. Gram negative organisms were 62.1% with Escherichia coli (25, 36.2%) as prevalent. Among the 37.8% gram positives, Staphylococcus aureus (18. 42.8%) was prevalent. Most of the E. coli strains showed highest resistance to ceftazidime (96%) and highest sensitivity to amikacin. The commonest gram-positive organism, Staphylococcus species were 100 % sensitive to vancomycin and linezolid and 100 % resistance to penicillin.  Conclusions: E. coli (gram negative) showed highest resistance to ceftazidime and sensitivity to amikacin. S. aureus (gram positive) was sensitive to vancomycin and linezolid and resistance to penicillin. An antibiogram for cancer patients helps the clinician to initiate an appropriate empirical antibiotic therapy to reduce mortality and morbidity.

scholarly journals Tracking the Fate of Porous Silicon Nanoparticles Delivering a Peptide Payload by Intrinsic Photoluminescence Lifetime

2018 ◽  
Vol 30 (35) ◽  
pp. 1802878 ◽  
Author(s):  
Yusung Jin ◽  
Dokyoung Kim ◽  
Hajung Roh ◽  
Sojeong Kim ◽  
Sazid Hussain ◽  
...  
Keyword(s):  
Porous Silicon ◽  
Silicon Nanoparticles ◽  
Porous Silicon Nanoparticles ◽  
Photoluminescence Lifetime

Efficacy of some medicated soaps and hand washes available in market

2021 ◽  
Vol 3 (1) ◽  
pp. 047-055
Author(s):  
Pimpliskar Mukesh ◽  
SoumyaGounder ◽  
Rahul Jadhav
Keyword(s):  
Broad Spectrum ◽  
Life Forms ◽  
Small Scale ◽  
Gram Positive ◽  
Consistent Finding ◽  
Gram Negative ◽  
Cross Transmission ◽  
Spectrum Activity ◽  
Significant Measure ◽  
Broad Spectrum Activity

Background: Handwashing is underlined as the absolute most significant measure to forestall cross-transmission of small-scale life forms and consequently to forestall nosocomial contaminations. Be that as it may, under routine emergency clinic practice consistent with this measure is still unsatisfactorily low, under half in many investigations distributed in the previous 20 years. This consistent finding is stressing because ongoing investigations have demonstrated that this degree of consistency won't decrease the danger of transmission of multi- medicate safe microscopic organisms in the emergency clinics. Results: In the present investigation effect of marketed hand washed namely Lifebuoy, Dettol and Savlon were tested on bacteria E. coli, S.aureus, S.pyogen, Klebshiella and, fungi Candida albicans. All the handwash at concentrated level found to be effective but only Dettol hand wash could give inhibitory action at 25ug/ml against Klebshiella while others at50ug/ml. Conclusions: Soapex and Dettol soap had broad spectrum activity as it inhibited the growth of Gram positive (Streptococcus pyogen) and Gram-negative (Escherichia coli). Liquid handwash such as Lifebuoy,Dettol and Savlon showed broad spectrum activity on both Gram-positive and Gram negative test microorganisms.

Serum biomarkers to differentiate Gram-negative, Gram-positive and fungal infection in febrile patients

2021 ◽  
Vol 70 (7) ◽  
Author(s):  
Dongguang Niu ◽  
Qian Huang ◽  
Fan Yang ◽  
Weiliang Tian ◽  
Chen Li ◽  
...  
Keyword(s):  
Bloodstream Infection ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Serum Levels ◽  
Serum Biomarker ◽  
Diagnostic Efficiency ◽  
Gram Positive ◽  
Gram Negative ◽  
Neutrophil Lymphocyte Ratio ◽  
Bacteria And Fungi

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G−) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G− group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G− group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725–0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708–0.796) in discriminating the G− group from G+ group. When discriminating the G− group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml−1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml−1. Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.

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