Getting Reinfections Despite Proper Antibiotic Doses? New Study Explains Why This Happens

Patients and doctors alike are familiar with a frustrating clinical scenario: An infection that seems cured after a full antibiotic course suddenly returns. Winter is specifically that time of the year when this happens frequently with many people, where a cold you nursed, treated cautiously and got over a month ago can come back in full swing today. Traditional explanations often point to antibiotic resistance, where bacteria evolve to withstand drugs designed to kill them. But a new study from Hebrew University of Jerusalem reveals another, less widely understood reason why infections can relapse even when antibiotics are given correctly: Antibiotic persistence. 

Persistence is a phenomenon where a small fraction of bacterial cells survives antibiotic treatment not through genetic resistance, but by entering a state that shields them temporarily from the drug's action. Antibiotics typically target actively growing bacteria, but persister cells evade this by halting growth in ways that make them nearly invisible to these drugs. These survivors can later "wake up," resume growth and cause a relapse of infection.

In research published in Science Advances, researchers led by Prof. Nathalie Balaban and PhD student Adi Rotem identified two fundamentally different modes by which bacteria survive antibiotics. One is the classic regulated, dormant state, and the other is a disrupted, dysregulated arrest that has its own vulnerabilities. Understanding these mechanisms may transform how clinicians approach antibiotic therapy and help reduce recurrent infections.

Also Read: Antimicrobial Resistance: These Are India's Most Overused Antibiotics

Why Infections Relapse Despite Proper Antibiotics

1. Persistence: Different from Genetic Resistance

Many people confuse antibiotic resistance with persistence, but they are distinct concepts. Resistance involves genetic changes that allow bacteria to multiply in the presence of an antibiotic, while persistence refers to a temporary survival state even when the bacteria are not growing. In this dormant or shutdown state, antibiotics are less effective because the metabolic processes they target are minimal or absent. 

The new study shows that failing to eradicate all bacterial cells during treatment isn't always about resistance genes, sometimes it's because certain cells enter survival modes that protect them until the antibiotic course ends. These survivors can then multiply again, leading to reinfection. 

2. Two Distinct Bacterial Shutdown Modes Identified

According to the research, bacterial populations can survive antibiotics through either of two growth-arrest pathways:

1. Regulated Growth Arrest (Dormancy): This is the classic explanation for persistence. Bacteria deliberately slow down and enter a controlled dormant state, conserving energy and becoming impervious to antibiotics that target active growth phases. Many chronic infections, such as those in urinary tracts or biofilm-associated implant infections, may involve these dormant persisters.
2. Disrupted Growth Arrest (Dysregulated Survival): Surprisingly, not all surviving bacteria enter a controlled dormant state. Some experience a disrupted, malfunctioning shutdown where normal cellular processes are chaotic and the cell membrane's stability is impaired. These cells survive antibiotics not through a protective strategy but by slipping into a stress-induced, dysfunctional condition that antibiotics can't easily kill.

Recognising these two modes helps explain why past studies of persister cells yielded conflicting results. They were observing different survival strategies of bacteria without realising it.

Also Read: What Happens If Antibiotics Stop Working? Doctor Explains The Nightmare Scenario

Clinical Implications: How This Understanding Could Improve Treatments

1. Tailored Therapeutic Strategies

The discovery of two persistence modes opens the possibility of targeted therapies tailored to the type of persister:

• Dormant persisters may be addressed with drugs that can reactivate metabolic processes before antibiotic action.
• Disrupted persisters might be susceptible to treatments that exploit their membrane instability.

Such precision strategies could ensure complete eradication of all bacterial cells during therapy courses, reducing reinfections.

2. Reducing Recurrence of Chronic Infections

Chronic infections like recurrent urinary tract infections or bacterial biofilms on medical implants often resist standard antibiotic courses. Understanding bacterial shutdown mechanisms helps explain why these recurrences occur and suggests clinical trials could focus on adjunctive therapies that prevent survival in both persistence modes.

3. Better Diagnostic Tools

Beyond treatment, the research points to potential new diagnostic approaches. Tests that distinguish persister types in a patient's infection might inform which antibiotic combinations or adjunct therapies are most likely to work, improving personalized treatment outcomes.

Getting reinfections despite proper antibiotic dosing has puzzled clinicians and patients alike for decades. Now, a landmark study reveals that the answer may lie in how bacteria survive, not by evolving resistance genes, but by entering one of two survival states that shield them from antibiotic attack. Recognizing these distinct shutdown modes could be a turning point in how infections are treated and prevented. By advancing therapeutic strategies that target both regulated and disrupted persister cells, science edges closer to reducing relapse rates and improving antibiotic effectiveness worldwide.

Disclaimer: This content, including advice, provides generic information only. It is in no way a substitute for a qualified medical opinion. Always consult a specialist or your own doctor for more information.