What is the duration for development of antibiotic resistance?

From the Guidelines

Antibiotic resistance can develop rapidly, sometimes within days or weeks of antibiotic exposure, and there is no evidence that taking antibiotics beyond symptom resolution reduces antibiotic resistance. The development of antibiotic resistance is a complex process that involves genetic mutations or the acquisition of resistance genes from other bacteria, allowing them to survive antibiotic treatments 1.

Key Points to Consider

• Bacteria become resistant through genetic mutations or by acquiring resistance genes from other bacteria, allowing them to survive antibiotic treatments.
• The spread of resistant bacteria is a global health concern because infections caused by resistant bacteria are harder to treat, requiring stronger antibiotics with potentially more side effects, longer hospital stays, and increased healthcare costs.
• Common antibiotics like amoxicillin, ciprofloxacin, or azithromycin are typically prescribed for specific durations (often 5-14 days depending on the infection) to ensure complete eradication of the bacterial infection.
• Stopping antibiotics early can leave some bacteria alive, giving them the opportunity to develop resistance.
• Taking antibiotics unnecessarily for viral infections like colds or flu contributes to resistance development.

Duration of Antibiotic Therapy

The American College of Physicians recommends appropriate use of short-course antibiotics in common infections, defining appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition 1.

• Shortening the duration of antibiotic therapy decreases overall antibiotic exposure, reducing the selection pressure for resistant organisms as well as a patient's risk for adverse effects from antibiotics.
• For several types of infections, studies and meta-analyses have shown that compared with longer courses of antibiotics, shorter courses show similar clinical outcomes with fewer drug-related adverse events 1.

Clinical Implications

The purpose of antibiotic therapy is to treat bacterial infections effectively while minimizing the risk of resistance development, and clinicians play a key role in antimicrobial stewardship, with quality improvement strategies able to improve antimicrobial prescribing 1.

• Clinicians should prescribe the right antibiotic at the right dose for the right duration for a specific condition, and when clinically safe and supported by evidence, shortening the duration of antibiotic therapy is recommended.
• Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition 1.

From the Research

Duration of Antibiotic Resistance Development

• The development of antibiotic resistance can occur rapidly, with some studies showing resistance emerging within 60 days of antibiotic exposure 2.
• Laboratory evolution experiments have demonstrated that clinically relevant resistance can arise quickly in priority Gram-negative ESKAPE pathogens, such as Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa 2.
• Adaptive resistance (AdR) is a type of resistance that can emerge as a consequence of concentration gradients or contact with subinhibitory concentrations of antibiotics, and can develop on longer time scales 3.
• The duration of antibiotic resistance development can vary depending on the type of bacteria, antibiotic, and environmental factors, making it challenging to predict and prevent resistance 4, 5, 6.

Factors Influencing Resistance Development

• The presence of mobile resistance genes in clinical bacterial isolates, soil, and human gut microbiomes can contribute to the rapid development of resistance 2.
• Epigenetic inheritance, population structure and heterogeneity, high mutation rates, gene amplification, efflux pumps, and biofilm formation are possible explanations for the development of adaptive resistance 3.
• The use of subinhibitory concentrations of antibiotics can select for resistant bacterial populations, leading to the emergence of resistance 3.

Implications for Antibiotic Development and Use

• The rapid development of resistance highlights the need for new and effective antibiotic candidates, as well as strategies to prevent and combat resistance 2, 6.
• Combining antibiotics with other therapies, such as pathogen-oriented therapy, phagotherapy, microbiota, and antivirulent therapy, may help to reduce the development of resistance 6.
• Understanding the mechanisms of resistance development and the factors that influence it can inform the development of more effective antibiotic treatments and strategies to mitigate resistance 4, 5, 3.