Nanobiotics: Challenging the anti-microbial perspective - The game changer?

2017 ◽  
Vol 6 (10) ◽  
pp. 5518 ◽  
Author(s):  
Deepak Narang ◽  
Jeevan Singh Tityal ◽  
Amit Jain ◽  
Reena Kulshreshtra ◽  
Fatima Khan
Keyword(s):  
Bacterial Resistance ◽  
Public Health Problem ◽  
Drug Resistant ◽  
European Science Foundation ◽  
Resistance Development ◽  
Bacterial Diseases ◽  
European Science ◽  
Tremendous Impact ◽  
New Strategies ◽  
Game Changer

Antibiotics are the most important medical inventions in human history and are the invaluable weapons to fight against various infectious diseases. Multi drug resistant microorganisms are becoming a serious issue and increasingly public health problem in present day scenario. Antibiotics are becoming less useful due to increasing bacterial resistance. Development of new and more powerful antibiotics leading to drastic pathogens response by developing resistance to the point where the most powerful drugs in our arsenal are no longer effective against them. New strategies for the management of bacterial diseases are urgently needed and nanomaterials can be a very promising approach. Nanobiotics uses nano-sized tools for the successful management bacterial diseases and to gain increased understanding of the complex underlying patho-physiology of disease. (European Science Foundation. Forward Look Nanomedicine: An EMRC Consensus Opinion 2005. Available online: http://www.esf.org (accessed on 15 July 2017). The application of nanotechnologies to medicine, or nanomedicine, which has already demonstrated its tremendous impact on the pharmaceutical and biotechnology industries, is rapidly becoming a major driving force behind ongoing changes in the antimicrobial field. Present review providing important insights on nanobiotics, and their preparation, mechanism of action, as well as perspectives on the opportunities and challenges in nanobiotics.

scholarly journals Organic-inorganic antimicrobial nanostructures for health care applications

2017 ◽  
Vol 4 (1-4) ◽  
pp. 66-80 ◽  
Keyword(s):  
Health Care ◽  
Metallic Nanoparticles ◽  
Public Health Problem ◽  
Klebsiella Pneumonia ◽  
Drug Resistant ◽  
Nanostructured Particles ◽  
Copper Gold ◽  
Health Care Applications ◽  
Bacteria And Fungi ◽  
New Strategies

In recent years, the drug resistant microorganisms are a serious and increasing public health problem. New strategies for controlling bacteria activity are urgently needed and nanomaterials can be a very promising approach, as the small size of the particle gives large surface area and consequently reactivity (and in many cases toxicity) increases substantially. The most tested metallic nanoparticles are silver, copper, gold, aluminum, titanium, iron, zinc, bismuth and others. Some of these metals have been coated onto several other materials. Another strategy is to incorporate these metals into a substrate such as polymethyl methacrylate forming organic-inorganic antimicrobial nanostructures. With respect to bacteria and fungi, the most frequent candidates for microbial experiments are: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, Bacillus subtilis among other species. The antimicrobial potential of these nanostructured particles, their mechanism of action and health care applications are presented and discussed at length in this review.

scholarly journals 44. Antibiotic Class-Based Distribution and Analysis of Reported Beta-Lactam Allergies amongst Hospitalized Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S45-S45
Author(s):  
Joseph Patrik Hornak ◽  
David Reynoso
Keyword(s):  
Bacterial Infections ◽  
Drug Resistant ◽  
Beta Lactam ◽  
Resistance Development ◽  
Texas Medical ◽  
University Of Texas ◽  
Icd 10 ◽  
Mrsa Infection ◽  
The University ◽  
Alternative Antibiotic

Abstract Background Reported β-lactam allergy (BLA) is very common, yet less than 10% of these patients exhibit true hypersensitivity. When faced with reported BLAs, physicians often choose alternative antibiotics which can be associated with C. difficile infection, drug-resistance development, poorer outcomes, & increased costs. Effective identification of these patients is necessary for subsequent, appropriate BLA “de-labeling.” Here, we conducted a single-center analysis of alternative antibiotic utilization amongst patients reporting BLA and compare the frequency of drug-resistant infections and C. difficile infection in allergic & non-allergic patients. Methods This is a retrospective review of adult patients hospitalized at The University of Texas Medical Branch from 1/1/2015 to 12/31/2019. Pooled electronic medical records were filtered by antibiotic orders and reported allergies to penicillins or cephalosporins. Patients with drug-resistant and/or C. difficile infection (CDI) were identified by ICD-10 codes. Microsoft Excel & MedCalc were used for statistical calculations. Results Data were available for 118,326 patients and 9.3% (11,982) reported a BLA, with the highest rates seen in those receiving aztreonam (85.9%, 530/617) & clindamycin (33.7%, 3949/11718). Amongst patients reporting BLA, high ratios-of-consumption (relative to all patients receiving antibiotics) were seen with aztreonam (7.0), clindamycin (2.7), cephalosporin/β-lactamase inhibitors (2.4), & daptomycin (2.1). Compared to the non-BLA population, BLA patients more frequently experienced MRSA infection (3.0% vs 1.5%, OR 1.99, 95% CI 1.79–2.23, p< 0.0001), β-lactam resistance (1.2% vs 0.6%, OR 2.07, 95% CI 1.72–2.49, p< 0.0001), and CDI (1.2% vs 0.7%, OR 1.85, 95% CI 1.54–2.23, p< 0.0001). Conclusion Our measured BLA rate matches approximate expectations near 10%. Moreover, these patients experienced significantly higher frequencies of drug-resistant bacterial infections and CDI. Targeted inpatient penicillin allergy testing stands to be particularly effective in those patients receiving disproportionately utilized alternative agents (e.g. aztreonam, clindamycin, daptomycin). β-lactam allergy “de-labeling” in these patients is likely a valuable antimicrobial stewardship target. Disclosures All Authors: No reported disclosures

scholarly journals Effect of Short-Term Carbapenem Restriction on Antimicrobial Susceptibility of Resistant Gram-Negative Bacilli in an ICU

2020 ◽  
Vol 41 (S1) ◽  
pp. s200-s201
Author(s):  
Mariana Melo ◽  
Raquel Bandeira ◽  
lio de Castro Giselle Dias ◽  
Braulio Couto
Keyword(s):  
High Mortality ◽  
Bacterial Resistance ◽  
Statistical Significance ◽  
Public Health Problem ◽  
Resistance Rate ◽  
Second Phase ◽  
Short Term ◽  
Intervention Phase ◽  
Carbapenem Resistant ◽  
The Impact

Background: Carbapenem-resistant GNB infections are a serious public health problem worldwide, particularly due to the high mortality associated with them and the low number of therapeutic options. One approach to this challenge is the development of antimicrobial stewardship programs. Objective: We evaluated the impact of a carbapenem restriction program on reducing of bacterial resistance in an intensive care unit (ICU). Methods: A retrospective study conducted in 2 phases in the 80-bed ICU of an acute-care public hospital in Minas Gerais, Brazil. The preintervention phase lasted 16 months (January 2018–April 2019) and the second phase (carbapenem restriction), after the intervention, lasted 4 months (May–August 2019). The intervention was defined as carbapenem-sparing and the use of meropenem was authorized in 3 situations: (1) treatment of serious infections documented by extended-spectrum β-lactamase–producing Enterobacteriacea (ESBL); (2) therapeutic failure with the use of another antimicrobial; and (3) infectious disease recommendation. Data were obtained through consultation of electronic medical records and microbiological results, as standardized by the CLSI, for patients with a >48-hour stay in the ICU and who met the criteria for healthcare-associated infection (HAI) according to the CDC NHSN definition. Results: Before the intervention, on average, 50 cultures were obtained with positive results for multidrug-resistant GNB–MER-GNB (SD, 12.2) and in the intervention phase, this number was 31 cultures (SD, 12.8; P = .010). Average carbapenem consumption decreased significantly with corresponding increase in cefepime consumption in the same period (Fig. 1). The ATB (DDD per 1,000 patient days) before the intervention for carbapenems was 110.6 (SD, 97.1) and for cefepime was 8.2 (SD, 5.9). In the intervention phase, the ATB for carbapenems was 44.7 (SD, 38.5; P = .015) and for cefepime it was 32.0 (SD, 20.3; P < .001). In terms of multidrug resistance rate, before the intervention, 95 of 149 of Acinetobacter (64%) were resistant and during the intervention, 13 of 30 Acinetobacter (43%) were resistant (P = .043). Other GNB (Klebsiella, Proteus, Escherichia coli, and Pseudomonas) reduced the resistance rate, but without statistical significance. We observed a reduction in the HAI rate per MDR-GNB (Fig. 2): before the intervention, it was 22.7 (SD, 5.5) and during the intervention phase it was 16.5 (SD, 7.7; P = .07), although this change did not reach statistical significance. Nevertheless, the ICU Klebsiella infection rate did significantly decrease; it was 5.5 (SD, 1.9) before the intervention and 2.4 (SD, 1.8) after the intervention (P = .009). Conclusions: Short-term carbapenem restriction may be an effective strategy to reduce the incidence of carbapenem-resistant GNB infections in the ICU. The scarce arsenal available for the treatment of MDR-GNB and the high mortality rate justify the growing need for stewardship programs in Brazilian ICUs.Funding: NoneDisclosures: None

scholarly journals Tackling Virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Therapeutic Agent ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Resistance Development

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.

scholarly journals COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics

2021 ◽  
Vol 22 (13) ◽  
pp. 6891
Author(s):  
João S. Rebelo ◽  
Célia P. F. Domingues ◽  
Francisco Dionisio ◽  
Manuel C. Gomes ◽  
Ana Botelho ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Human Microbiome ◽  
Antibiotic Resistance Genes ◽  
Public Health Problem ◽  
Small World ◽  
Physical Contact ◽  
Hygiene Measures

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal–Wallis and Dunn’s pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.

scholarly journals In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride

2021 ◽  
Vol 14 (6) ◽  
pp. 517
Author(s):  
Joseph Blondeau ◽  
Heleen DeCory
Keyword(s):  
Staphylococcus Epidermidis ◽  
Benzalkonium Chloride ◽  
Bacterial Species ◽  
Drug Resistant ◽  
Resistance Development ◽  
Aureus Isolate ◽  
Killing Activity ◽  
Time Kill ◽  
Variable Impact

Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of Staphylococcus epidermidis (n = 4), Staphylococcus aureus (n = 3), Haemophilus influenzae (n = 2), and Pseudomonas aeruginosa (n = 2) in time-kill experiments of 180 min duration. With the exception of one S. aureus isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one P. aeruginosa isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log10 CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of P. aeruginosa (<5 min) and H. influenzae (<120 min), and approached 3-log kills of S. aureus. BAK alone demonstrated concentration-dependent killing of S. epidermidis, S. aureus and H. influenzae, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except P. aeruginosa and a variable impact on S. aureus. The greatest reductions in AUKC were observed among H. influenzae (8-fold) and S. epidermidis (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant S. epidermidis. Greater killing activity may help prevent resistance development and/or help treat resistant organisms.

Optimized loading dose strategies for bedaquiline when restarting interrupted drug-resistant tuberculosis treatment

2022 ◽  
Author(s):  
Simon E Koele ◽  
Stijn W van Beek ◽  
Gary Maartens ◽  
James C. M. Brust ◽  
Elin M Svensson
Keyword(s):  
Treatment Interruption ◽  
Loading Dose ◽  
Drug Resistant ◽  
Time Curve ◽  
Resistance Development ◽  
Drug Resistant Tuberculosis ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Starting Point ◽  
One Year

Interruption of treatment is common in drug-resistant tuberculosis patients. Bedaquiline has a long terminal half-life therefore, restarting after an interruption without a loading dose could increase the risk of suboptimal treatment outcome and resistance development. We aimed to identify the most suitable loading dose strategies for bedaquiline restart after an interruption. A model-based simulation study was performed. Pharmacokinetic profiles of bedaquiline and its metabolite M2 (associated with QT-prolongation) were simulated for 5000 virtual patients for different durations and starting points of treatment interruption. Weekly bedaquiline area under the concentration-time curve (AUC) and M2 maximum concentration (Cmax) deviation before interruption and after reloading were assessed to evaluate the efficacy and safety respectively of the reloading strategies. Bedaquiline weekly AUC and M2 Cmax deviation were mainly driven by the duration of interruption and only marginally by the starting point of interruption. For interruptions with a duration shorter than two weeks, no new loading dose is needed. For interruptions with durations between two weeks and one month, one month and one year, and longer than one year, reloading periods of three days, one week, and two weeks, respectively, are recommended. This reloading strategy results in an average bedaquiline AUC deviation of 1.88% to 5.98% compared with -16.4% to -59.8% without reloading for interruptions of two weeks and one year respectively, without increasing M2 Cmax. This study presents easy-to-implement reloading strategies for restarting a patient on bedaquiline treatment after an interruption.

scholarly journals Effects of low concentrations of erythromycin, penicillin, and virginiamycin on bacterial resistance development in vitro

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Beilei Ge ◽  
Kelly J. Domesle ◽  
Qianru Yang ◽  
Shenia R. Young ◽  
Crystal L. Rice-Trujillo ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Resistance Development ◽  
Low Concentrations ◽  
Development In Vitro
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