How can antibiotic resistance genes be effectively managed and prevented?

Managing and Preventing Antibiotic Resistance Genes

Implement comprehensive antimicrobial stewardship programs focused on optimizing appropriate antibiotic use—not simply restricting access—as the cornerstone strategy, combined with robust surveillance systems tracking both resistance patterns and antibiotic consumption, while simultaneously strengthening infection prevention to reduce the need for antibiotics in the first place. 1, 2

Core Strategic Framework

The management of antibiotic resistance genes requires a multidisciplinary approach addressing three interconnected domains: antimicrobial stewardship, surveillance infrastructure, and infection prevention. 3

Antimicrobial Stewardship Programs

Every hospital must establish a Drug and Therapeutics Committee with authority over antimicrobial policy, supported by a written antibiotic formulary accessible to all prescribers. 2 This committee should include clinical pharmacists as core members with hospital-wide responsibility for measuring and analyzing antibiotic consumption. 2

Key operational elements:

• Appoint an Antibiotic Coordinator to collect usage data, perform compliance audits, and report prescribing quality to the committee 2
• Reserve specific antibiotics (carbapenems, glycopeptides, fourth-generation cephalosporins, oxazolidinones) for defined indications only 2
• Track antibiotic consumption using pharmacy databases, measuring usage in Defined Daily Doses per 100 patient-days, and investigate reasons for high consumption patterns 2
• Optimize pharmacokinetic/pharmacodynamic properties by selecting antibiotics with appropriate dosing intervals and concentrations to maximize bacterial killing while minimizing resistance selection 1, 2

Surveillance Systems

Establish comprehensive surveillance tracking both antibiotic usage patterns and resistance prevalence among major pathogens. 3, 1 This dual surveillance approach is essential to define the scale of resistance problems and assess the impact of containment strategies. 3

Critical surveillance components:

• Analyze annual antimicrobial susceptibility data with duplicates removed and feed results back to prescribers 2
• Combine usage data with local resistance epidemiology to guide empiric therapy choices 2
• Deploy rapid diagnostic tests that detect not only bacteria but also antibiotic resistance genes to differentiate bacterial from viral infections before prescribing 3, 1, 2
• Strengthen genomic surveillance capacity following the COVID-19 pandemic model, which demonstrated the power of high-resolution genomic monitoring for tracking resistance mechanisms and transmission dynamics 3

Infection Prevention Strategies

Every infection prevented is one that needs no treatment—making infection prevention the most cost-effective strategy implementable in all settings, even where resources are limited. 3

Essential prevention measures:

• Meet minimum infection control staffing: one infection control nurse per 250 acute-care beds and one physician per 1000 beds 2
• Promote standard infection control precautions with regular compliance audits 2
• Implement vaccination programs to reduce infection incidence and subsequent antibiotic need, targeting major pathogens involved in community-acquired infections (Streptococcus pneumoniae, Haemophilus influenzae, influenza viruses, respiratory syncytial virus) 3, 1

Community-Based Interventions

Target respiratory tract infections in community settings as the highest priority intervention point, where 20-50% of antibiotic prescribing is unnecessary. 1, 2 In the United States, 55% of antibiotics prescribed for acute respiratory tract infections exceed what is needed to treat actual bacterial infections. 1

Address prescribing pressures systematically:

• Develop active collaboration between medical professionals, patient representatives, and behavioral change experts (psychologists, sociologists) to address the multiple pressures driving inappropriate prescribing 1, 2
• Provide primary care physicians with evidence-based prescribing guidelines, diagnostic stewardship tools, and strategies to address patient pressure for antibiotics 1, 2
• Deploy rapid diagnostic tests (such as rapid antigen tests for group A streptococci in pharyngitis) to increase appropriate treatment and reduce unnecessary antibiotic use 3

Audit and Feedback Mechanisms

Initiate continuous audit where poor performance is revealed by resistance surveillance and usage data, providing prescribers with comparative feedback showing their prescribing patterns against guidelines. 1, 2 Feedback to prescribers helps them modify practices based on evidence, though this element is seldom mentioned in many programs. 3

Understanding Resistance Gene Transmission

Resistance genes are frequently located on mobile genetic elements that can be inherited by progeny and transferred between bacterial species, creating persistent reservoirs of multidrug-resistant organisms. 4, 5 These mobile elements often carry genes encoding resistance to multiple unrelated antimicrobial classes, conferring multidrug resistance. 4

Critical ecological considerations:

• Resistance does not necessarily evolve in pathogenic organisms being targeted—low-virulence commensal bacteria in gastrointestinal or respiratory tracts may develop resistance to survive antibiotic exposure, then transmit these mechanisms to more virulent species 4
• Once antibiotic exposure stops, resistant bacteria do not necessarily revert to being susceptible—the encoding mechanism is inherited by future bacterial progeny 4
• The gastrointestinal tract serves as a major reservoir for antibiotic-resistant organisms, where resistant bacteria develop and persist due to antibiotic exposure and can acquire mobile genetic elements transferable to other bacterial species 4

One Health Approach

Addressing antimicrobial resistance requires a holistic One Health approach because antimicrobials used in animals may be the same or similar to those used for humans, and resistant bacteria arising in humans, animals, or the environment may spread across all domains. 3 Antibacterial and antifungal use in animal and agricultural industries aggravates selective pressure on microbes. 3

Global cooperation requirements:

• Developed countries must support resistance control in developing regions through quality control assistance, marketing approval guidance, and healthcare worker education, as resistance in one region threatens all regions through international travel 2
• Address over-the-counter availability in developing countries, combined with poor quality control and substandard antibiotic formulations, which accelerates resistance emergence 1

Common Pitfalls to Avoid

Do not select therapeutic alternatives without evidence-based rationale, as this promotes resistance and shifts rather than contains costs. 1 Economic initiatives alone are insufficient—countries implementing non-reimbursement policies or prescriber-targeted economic measures achieved only temporary reductions in antibiotic use; sustainability requires comprehensive programs. 1

Avoid viewing resistance control as an all-or-nothing approach; prioritize interventions hierarchically rather than attempting everything simultaneously. 1 The best strategies for combating antimicrobial resistance are not definitively established and likely vary based on local culture, policy, and routine clinical practice. 3

Do not underestimate the problem in your own institution—although most clinicians are aware of antimicrobial resistance, most underestimate this problem in their own hospital. 3

Patient and Public Education

Raising awareness of antimicrobial resistance and promoting behavioral change through public communication programs targeting different audiences in human health, animal health, and agricultural practice, as well as consumers, are critical to tackling this issue. 3

Patient counseling must emphasize:

• Antibacterial drugs should only be used to treat bacterial infections, not viral infections like the common cold 6
• Skipping doses or not completing the full course of therapy may decrease treatment effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable by the same or other antibacterial drugs in the future 6

Research Priorities

Promote further research to improve knowledge of infectious diseases and the complexities of resistance development and spread, which is necessary to improve resistance control program design. 3 Major gaps remain in our understanding, including:

• The reversibility of resistance with optimized antibiotic use remains unestablished, necessitating intervention and case-control studies 1
• Clinical trials defining minimum treatment duration for common infections are needed 1
• Mathematical models predicting resistance extension with antibiotic use changes require validation 1
• Impact measurement of resistance on mortality, morbidity, and quality of life needs standardized methodologies 1

3, 1, 2, 4, 6, 5