Can Nanoparticles Help in the Battle against Drug-Resistant Bacterial Infections in “Post-Antibiotic Era”?

2022 ◽  
pp. 175-213
Author(s):  
Niranjana Sri Sundaramoorthy ◽  
Saisubramanian Nagarajan
2013 ◽  
Author(s):  
Andrew M. Gulick ◽  
Thomas A. Russo ◽  
L. W. Schultz ◽  
Timothy C. Umland

Author(s):  
Daniel Berman

How can we prevent the rise of resistance to antibiotics? In this video, Daniel Berman,  Nesta Challenges, discusses the global threat of AMR and how prizes like the Longitude Prize can foster the development of rapid diagnostic tests for bacterial infections, helping to contribute towards reducing the global threat of drug resistant bacteria. Daniel outlines how accelerating the development of rapid point-of-care tests will ensure that bacterial infections are treated with the most appropriate antibiotic, at the right time and in the right healthcare setting.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S45-S45
Author(s):  
Joseph Patrik Hornak ◽  
David Reynoso

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


Spinal Cord ◽  
2021 ◽  
Author(s):  
Lorenz Leitner ◽  
Shawna McCallin ◽  
Thomas M. Kessler

AbstractBacterial infections are the leading cause of death in people with a spinal cord injury (SCI). Bacteriophages (phages) are viruses that solely infect and kill bacteria. The idea of using phages to treat bacterial infections, i.e., phage therapy, is very promising and potentially allows a more specific and personalized treatment of bacterial infections than antibiotics. While multi-drug resistant infections affect individuals from the general population, alternative therapeutic options are especially warranted in high-risk populations, such as individuals with SCI. However, more clinical data must be collected before phage therapy can be implemented in clinical practice, with numerous possible, subsequent applications.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)


2020 ◽  
Vol 17 (11) ◽  
pp. 1168-1176
Author(s):  
Dennapa SAELOH ◽  
Monton VISUTTHI ◽  
Marisa LEEHA ◽  
Surasak LIMSUWAN ◽  
Supayang Piyawan VORAVUTHIKUNCHAI

Acinetobacter baumannii (A. baumannii) has been known as a major cause of nosocomial bacterial infections worldwide. The bacteria are increasingly associated with a broad spectrum of antibiotic resistance, and this has become a widespread concern in a variety of hospitals.Antibiotic development and alternative treatment have become priorities for the treatment of bacterial infections.This study investigated the efficacy of meropenem in combination with five ethanolic extracts of plants in Myrtaceae against extensively drug-resistant (XDR) A. baumannii. The resistant phenotype was previously determined by microdilution method. XDR-A. baumannii strains showed resistance to meropenem with the minimum inhibitory concentration (MIC) in a range of 16 - 128 µg/mL, whereas the MIC value of all extracts, including Calistemon lancealatus, Eucalyptus citridora, Rhodomytus tomentasa, Syzygium cumini, and Xanthortemon chrysanthus, was over 1,000 µg/mL. Interestingly, all extracts potentiated the activity of the antibiotic by reducing the MIC values of the antibiotic. Xanthortemon chrysanthus extract displayed excellent synergism against the bacteria by decreasing the MIC value of the drug greater than 8-fold. In addition, the extract, at concentrations of 31.25, 62.5, 125, 250, 500, and 1,000 µg/mL, obviously increased the inhibitory effect of meropenem (1/4´MIC) against A. baumannii. The percentage of bacterial growth inhibition by combination was 87.9, 88.8, 91.8, 93.6, 99.9, and 100, respectively. The results supported that the extract could improve the activity of ineffective antibiotics against drug-resistant pathogens.Therefore, the findings may serve as therapeutic options for XDR-A. baumannii infections in the future.


2021 ◽  
Author(s):  
Iris K Lee ◽  
Daniel A Jacome ◽  
Joshua K Cho ◽  
Vincent Tu ◽  
Anthony Young ◽  
...  

Recently, several molecular imaging strategies have developed to image bacterial infections in humans. Nuclear approaches, specifically positron emission tomography (PET), affords sensitive detection and the ability to non-invasively locate infections deep within the body. Two key radiotracer classes have arisen: metabolic approaches targeting bacterial specific biochemical transformations, and antibiotic-based approaches that have inherent selectivity for bacteria over mammalian cells. A critical question for clinical application of antibiotic radiotracers is whether resistance to the template antibiotic abrogates specific uptake, thus diminishing the predictive value of the diagnostic test. We recently developed small-molecule PET radiotracers based on the antibiotic trimethoprim (TMP), including [11C]-TMP, and have shown their selectivity for imaging bacteria in preclinical models. Here, we measure the in vitro uptake of [11C]-TMP in pathogenic susceptible and drug-resistant bacterial strains. Both resistant and susceptible bacteria showed similar in vitro uptake, which led us to perform whole genome sequencing of these isolates to identify the mechanisms of TMP resistance that permit retained radiotracer binding. By interrogating these isolate genomes and a broad panel of previously sequenced strains, we reveal mechanisms where uptake or binding of TMP radiotracers can potentially be maintained despite the annotation of genes conferring antimicrobial resistance. Finally, we present several examples of patients with both TMP-sensitive and drug-resistant infections in our first-in-human experience with [11C]-TMP. This work underscores the ability of an antibiotic radiotracer to image bacterial infection in patients, which may allow insights into human bacterial pathogenesis, infection diagnosis, and antimicrobial response monitoring.


2014 ◽  
Author(s):  
Andrew M. Gulick ◽  
Thomas A. Russo ◽  
L. W. Schulz ◽  
Timothy C. Umland

2020 ◽  
Vol 22 (4) ◽  
pp. 287-300
Author(s):  
Elizaveta D. Shedko ◽  
O.Yu. Timoshina ◽  
Ilya Sulejmanovich Azyzov

Colistin and polymyxin B are the “last reserve” antimicrobials for the treatment of extensively drug-resistant Gram-negative bacterial infections. The rapidly increasing prevalence of polymyxin resistance mediated by the mcr gene localized on plasmid DNA currently poses a high epidemiological threat. In order to control a distribution of mcr genes, it is necessary to develop highly accurate, highly sensitive and easy-to-use diagnostic tools. This paper provides a review of the most relevant studies on the molecular epidemiology as well as current approaches to microbiological and molecular detection of mcr group genes.


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