scholarly journals Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Elizabeth M. Adamowicz ◽  
William R. Harcombe
Keyword(s):  
Antimicrobial Resistance ◽  
Combination Therapy ◽  
Bacterial Infections ◽  
Interaction Patterns ◽  
Weakest Link ◽  
Infection Treatment ◽  
Additional Challenge ◽  
Global Threat ◽  
Multiple Drugs ◽  
Antibiotic Interactions

ABSTRACT With the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, in which multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for the treatment of bacterial infections due to difficulties in selecting the correct combinations and dosages. An additional challenge in infection treatment is the polymicrobial nature of many infections, which may respond to antibiotics differently than a monoculture pathogen. This study tests whether patterns of antibiotic interactions (synergy, antagonism, or independence/additivity) in monoculture can be used to predict antibiotic interactions in an obligate cross-feeding coculture. Using our previously described weakest-link hypothesis, we hypothesized antibiotic interactions in coculture based on the interactions we observed in monoculture. We then compared our predictions to observed antibiotic interactions in coculture. We tested the interactions between 10 previously identified antibiotic combinations using checkerboard assays. Although our antibiotic combinations interacted differently than predicted in our monocultures, our monoculture results were generally sufficient to predict coculture patterns based solely on the weakest-link hypothesis. These results suggest that combination therapy for cross-feeding multispecies infections may be successfully designed based on antibiotic interaction patterns for their component species.

scholarly journals Weakest link dynamics predict apparent antibiotic interactions in a model cross-feeding community

2020 ◽  
Author(s):  
Elizabeth M. Adamowicz ◽  
William R. Harcombe
Keyword(s):  
Antimicrobial Resistance ◽  
Combination Therapy ◽  
Bacterial Infections ◽  
Interaction Patterns ◽  
Weakest Link ◽  
Infection Treatment ◽  
Additional Challenge ◽  
Global Threat ◽  
Multiple Drugs ◽  
Antibiotic Interactions

AbstractWith the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, wherein multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for the treatment of bacterial infections due to difficulties in selecting the correct combinations and dosages. An additional challenge in infection treatment is the polymicrobial nature of many infections, which may respond to antibiotics differently than a monoculture pathogen. This study tests whether patterns of antibiotic interactions (synergy, antagonism, or independence/additivity) in monoculture can be used to predict antibiotic interactions in an obligate cross-feeding co-culture. Using our previously described weakest link hypothesis, we hypothesized antibiotic interactions in co-culture based on the interactions we observed in monoculture. We then compared our predictions to observed antibiotic interactions in co-culture. We tested the interactions between ten previously identified antibiotic combinations using checkerboard assays. Although our antibiotic combinations interacted differently than predicted in our monocultures, our monoculture results were generally sufficient to predict co-culture patterns based solely on the weakest link hypothesis. These results suggest that combination therapy for cross-feeding multispecies infections may be successfully designed based on antibiotic interaction patterns for their component species.

scholarly journals Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
James V. Rogers ◽  
Veronica L. Hall ◽  
Charles C. McOsker
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Defense Mechanism ◽  
Treatment Options ◽  
Bacterial Biofilms ◽  
Host Immune System ◽  
New Antibiotics ◽  
Financial Burdens ◽  
Global Threat

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.

scholarly journals Combating antimicrobial resistance using antimicrobial combination therapy and β–lactamase inhibitors

2018 ◽  
Vol 12 (02.1) ◽  
pp. 14S
Author(s):  
Bassam El-Hafi ◽  
Sari Shawki Rasheed ◽  
Noor A Salloum ◽  
Antoine Abou Fayad ◽  
George F Araj ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antimicrobial Resistance ◽  
Combination Therapy ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Approaches ◽  
Expression Levels ◽  
Gene Expression Levels

Introduction: The range of antimicrobial agents used to treat bacterial infections is becoming limited with the constant increase in antimicrobial resistance (AMR). Several genetic factors underlie AMR, including β-lactamase-encoding genes such as blaCTXM-15 that confers resistance to third-generation cephalosporins, and blaOXA-48, blaNDM-1, and blaKPC-2 that confer resistance to carbapenems. Remaining treatment approaches for such resistant infections include antimicrobial combination therapy and the use of β-lactamase inhibitors. This study assesses the molecular effects of such treatment approaches on antimicrobial resistant Enterobacteriaceae clinical isolates in vitro and in vivo. Methodology: Nine clinical Enterobacteriaceae isolates were included in the study. One harboring blaCTXM-15, one harboring blaOXA-48, one harboring blaKPC-2, two harboring blaNDM-1 and blaCTXM-15, and four harboring blaOXA-48 and blaCTXM-15. Minimal inhibitory concentrations were determined for carbapenems with β-lactamase inhibitors: avibactam, Ca-EDTA, and relebactam. Synergism between antibiotic combinations was determined by double disc diffusion when using colistin with several antibiotics. In vitro and in vivo gene expression levels were done on these combinations with and without inhibitors. Results: The use of meropenem, imipenem, and ertapenem with the selected β-lactamase inhibitors restored isolate susceptibility in 100%, 87.5%, and 25% of the cases, respectively. Antimicrobial synergism was mostly detected between colistin and meropenem, fosfomycin, or tigecycline. Survival studies revealed the survival of most mice receiving antimicrobial combination therapy with inhibitors as compared to the controls. Overall gene expression levels of resistance genes were variable depending on treatment. Conclusions: The threat of antibiotic resistant bacterial infections remains viable; however, different approaches to therapy are available.

scholarly journals Antimicrobial Resistance of Streptococcus uberis Isolated from Bovine Mastitis: A Review

2021 ◽  
Author(s):  
Tingrui Zhang ◽  
Linli Tao ◽  
Sukolrat Boonyayatra ◽  
Guoyi Niu
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Animal Health ◽  
Bovine Mastitis ◽  
Subclinical Mastitis ◽  
Economic Losses ◽  
Health Crisis ◽  
The Public ◽  
Streptococcus Uberis ◽  
Global Threat

Bovine mastitis is one of the common diseases resulting in high economic losses in the dairy industry. Streptococcus uberis, the environmental or contagious pathogen, is one of the most frequently identified bacteria causing clinical and subclinical mastitis. Antimicrobials are commonly used to control bacterial infections in dairy cattle. The emergence of antimicrobial resistance (AMR) bacteria made the treatment of this disease by antimicrobials a challenge. Currently, AMR is a global threat to both human and animal health. This review summarizes the AMR profiles of S. uberis collected worldwide between the years 2000-2020. Most of the studies included in this review were from Europe, Estonia, Canada, Danish, Switzerland and Czech. In general, S. uberis is highly susceptible to β-lactam antimicrobials, whereas resistance to tetracyclines, macrolides, aminoglycosides antimicrobials occurred in most countries. The isolates against most antimicrobials presented an increasing pattern over time. It highlights that monitoring the AMR of S. uberis is crucial to reduce the public health crisis.

Recent Review on Subclass B1 Metallo-β-lactamases Inhibitors: Sword for Antimicrobial Resistance

2019 ◽  
Vol 20 (7) ◽  
pp. 756-762 ◽  
Author(s):  
Aditi Kaushik ◽  
Manish Kaushik ◽  
Viney Lather ◽  
J.S. Dua
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Antimicrobial Resistance ◽  
Global Health ◽  
Human Health ◽  
Microbial Pathogens ◽  
Present Review ◽  
Drug Molecules ◽  
Global Threat ◽  
Powerful Strategy

An emerging crisis of antibiotic resistance for microbial pathogens is alarming all the nations, posing a global threat to human health. The production of the metallo-β-lactamase enzyme is the most powerful strategy of bacteria to produce resistance. An efficient way to combat this global health threat is the development of broad/non-specific type of metallo-β-lactamase inhibitors, which can inhibit the different isoforms of the enzyme. Till date, there are no clinically active drugs against metallo- β-lactamase. The lack of efficient drug molecules against MBLs carrying bacteria requires continuous research efforts to overcome the problem of multidrug-resistance bacteria. The present review will discuss the clinically potent molecules against different variants of B1 metallo-β-lactamase.

Re-challenging antibiotic resistance with Daniel Berman

2020 ◽  
Author(s):  
Daniel Berman
Keyword(s):  
Bacterial Infections ◽  
Point Of Care ◽  
Healthcare Setting ◽  
Rapid Diagnostic Tests ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Global Threat ◽  
The Right ◽  
Point Of Care Tests

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.

scholarly journals Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Author(s):  
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Private Investment ◽  
Therapeutic Index ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Delivery Systems ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

scholarly journals Emerging Options for the Diagnosis of Bacterial Infections and the Characterization of Antimicrobial Resistance

2021 ◽  
Vol 22 (1) ◽  
pp. 456
Author(s):  
Simone Rentschler ◽  
Lars Kaiser ◽  
Hans-Peter Deigner
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Point Of Care ◽  
Rapid Identification ◽  
Adequate Treatment ◽  
Resistance Patterns ◽  
Detection And Diagnosis ◽  
Patient Prognosis ◽  
Point Of Care Detection

Precise and rapid identification and characterization of pathogens and antimicrobial resistance patterns are critical for the adequate treatment of infections, which represent an increasing problem in intensive care medicine. The current situation remains far from satisfactory in terms of turnaround times and overall efficacy. Application of an ineffective antimicrobial agent or the unnecessary use of broad-spectrum antibiotics worsens the patient prognosis and further accelerates the generation of resistant mutants. Here, we provide an overview that includes an evaluation and comparison of existing tools used to diagnose bacterial infections, together with a consideration of the underlying molecular principles and technologies. Special emphasis is placed on emerging developments that may lead to significant improvements in point of care detection and diagnosis of multi-resistant pathogens, and new directions that may be used to guide antibiotic therapy.

Epidemiology, risk factors and antimicrobial resistance of Escherichia coli bacteremia

2021 ◽  
Vol 11 (Number 2) ◽  
pp. 58-67
Author(s):  
Mahjuba Umme Salam ◽  
Selina Yasmin ◽  
Md. Rashedul Haque ◽  
Sharmin Ahmed ◽  
Shahidul Alam ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Antibiotic Susceptibility ◽  
Antimicrobial Agents ◽  
Blood Stream Infection ◽  
Incidence Rates ◽  
Diffusion Method ◽  
Antibiotic Susceptibility Test ◽  
Multiple Drugs

Background: Escherichia coli is a common causative of blood stream infection having potentials to produce significant morbidity and mortality. This organism also has the ability to develop resistance against antimicrobial agents. Knowing its epidemiology, risk factors and antimicrobial resistance patterns can help preventing and managing bacteremia caused by this organism. Materials and methods: This was across sectional observational study carried out from February 2017 to February 2018 on 64 blood culture positive Escherichia coli infected patients admitted in Medicine inpatient of a medical college hospital. Age, sex, mode of acquisition of infection, history of prior empiric antibiotic treatment, duration of hospital stay, development of complication were observed and noted. Antibiotic susceptibility test for all isolates was performed by Kirby-Bauer disc diffusion method. Predesigned semi-structured data collection from was used and collected data were analyzed manually and expressed in descriptive statistical terms. Results: Of the 64 enrolled patients, 47(73.43%) were female. Average age of affection was 53.48±20.65 years and increased incidence rates (51.56%) was observed at age >60 years. Infection was communityacquired in 35.84% cases and urinary tract infection was the most frequent (46.3) risk factor. More than eighty seven percent of samples showed resistance to at least one antimicrobial agent and resistance to multiple drugs was associated with complications. Conclusion: Escherichia coli bacteremia has high incidence rates for antimicrobial resistance and mortality. Continuous surveillance and antibiotic susceptibility pattern monitoring is essential to develop regional antibiotic therapy protocols.

scholarly journals Technologies to address antimicrobial resistance

2018 ◽  
Vol 115 (51) ◽  
pp. 12887-12895 ◽  
Author(s):  
Stephen J. Baker ◽  
David J. Payne ◽  
Rino Rappuoli ◽  
Ennio De Gregorio
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Membrane Vesicles ◽  
Multidrug Resistant ◽  
Outer Membrane Vesicles ◽  
Resistant Bacteria ◽  
Multiple Stakeholders ◽  
Global Challenge ◽  
Life Threatening ◽  
Bacterial Outer Membrane

Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.

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