Emerging gram-negative antibiotic resistance: daunting challenges, declining sensitivities, and dire consequences
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Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing
Published on: July 7, 2020
1Department of Pulmonary and Critical Care Medicine, James J Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA. robert.siegel@va.gov
Abstract:
Emerging antibiotic resistance has created a major public health dilemma, compounded by a dearth of new antibiotic options. Multidrug-resistant Gram-negative organisms have received less attention than Gram-positive threats, such as methicillin-resistant Staphylococcus aureus, but are just as menacing. Pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii employ a variety of resistance mechanisms and are associated with dangerous nosocomial outbreaks. In some cases these pathogens have expressed resistance to all clinically available compounds. The emergence of extended-spectrum beta-lactamase-producing organisms in the community has raised alarm. Furthermore, the carbapenems, currently the most successful class of antibiotics, are showing signs of vulnerability. While the search for new antibiotic options continues, there is urgent need to employ strategies that will slow the development of resistance to the current armamentarium, such as avoiding prolonged antibiotic use or under-dosing, using pharmacokinetic and pharmacodynamic principles to choose dosing regimens, and encouraging early and aggressive empirical therapy, followed by de-escalation and narrowing the antimicrobial spectrum when culture results become available.
Insights
Antibiotic resistance is a growing crisis, especially with Gram-negative bacteria. New strategies are urgently needed to preserve existing antibiotics and combat resistant infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Public Health
Background:
- Emerging antibiotic resistance poses a significant public health threat.
- Multidrug-resistant Gram-negative organisms, like Pseudomonas aeruginosa and Acinetobacter baumannii, are increasingly problematic.
- These pathogens exhibit resistance to multiple antibiotics, complicating treatment and leading to nosocomial outbreaks.
Purpose of the Study:
- To highlight the escalating threat of antibiotic resistance, particularly from Gram-negative pathogens.
- To underscore the limited development of new antibiotic therapies.
- To emphasize the critical need for strategies to preserve the efficacy of current antibiotics.
Main Methods:
- Review of current literature on antibiotic resistance mechanisms in Gram-negative bacteria.
- Analysis of clinical implications of multidrug-resistant organisms.
- Discussion of strategies to mitigate antibiotic resistance development.
Main Results:
- Gram-negative pathogens demonstrate diverse and potent resistance mechanisms.
- Some pathogens are resistant to all available antibiotics.
- Carbapenem antibiotics, a crucial class, are showing signs of reduced effectiveness.
- Extended-spectrum beta-lactamase (ESBL)-producing organisms are emerging in community settings.
Conclusions:
- Urgent implementation of antibiotic stewardship is necessary to slow resistance.
- Strategies include optimizing dosing, avoiding prolonged or sub-therapeutic use.
- Early, targeted antibiotic therapy based on culture results is recommended.
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