When treating Lyme disease, a common challenge is not just choosing the right antibiotic—but making sure a patient can tolerate it. In my practice, I’ve found that a common-sense, flexible approach to dosing often makes the difference between failure and success, especially for patients who struggle with side effects or sensitivities.

When Standard Doses Don’t Work

I once treated a patient who had been reluctant to restart antibiotics after a difficult first experience with treatment. He had stopped due to significant side effects. Understandably, he was hesitant to try again. But when we began with a lower starting dose, he was able to tolerate it and continue his course of treatment—something that hadn’t been possible before.

This is not an uncommon scenario.

When the Gut Gets in the Way

Many of my patients have underlying gastrointestinal conditions that make it hard to tolerate antibiotics, including:

• Gastroparesis
• Leaky gut
• Diarrhea, constipation, or IBS
• Candida and yeast overgrowth

Others have had Herxheimer reactions—a temporary but intense worsening of symptoms caused by the die-off of spirochetes during antibiotic therapy. This reaction, also known as the Jarisch-Herxheimer Reaction (JHR), is most often seen in infections caused by spirochetes like Lyme disease, syphilis, or relapsing fever. It can be overwhelming for patients who are already dealing with chronic symptoms.

I’ve also had patients who can’t swallow pills or who can’t tolerate liquid formulations either, making treatment especially tricky.

Ruling Out Other Causes

Before assuming antibiotics are the root of the problem, I often refer patients to specialists to evaluate for underlying causes of their medication intolerance:

• A gastroenterologist can help rule out structural or motility issues in the stomach or gut.

• Other specialists may help assess for autonomic nervous system disorders, which can disrupt digestion and drug absorption.

By evaluating these possibilities, we can create a treatment plan that’s both effective and tolerable.

Weighing Risks and Benefits

I also see patients who have tried dietary changes and alternative medicine, but remain ill. These patients often face a crossroads—deciding whether to try antibiotics again. I help them weigh the risks of antibiotic therapy against the risk of remaining sick from an untreated or under-treated infection.

Some still choose not to pursue antibiotics, which I respect. I continue to support these patients by recommending that they avoid alcohol and processed sugars, which may worsen gut symptoms and promote inflammation.

What I Do Differently: Low and Slow

For patients open to treatment, I follow a “start low, go slow” approach.

Here are some ways I adjust medications to improve tolerability:

• Doxycycline: I’ve started some patients at 25–50 mg once daily, instead of the typical 100 mg twice daily. I may use a liquid formulation to make dosing easier.

• Cefuroxime: I’ve lowered the dose from 500 mg twice daily to 250 mg twice daily.

• Azithromycin (Zithromax): Given its long half-life, I sometimes prescribe 250 mg every other day or every third day.

• Atovaquone: Instead of the usual 750 mg twice a day, I’ve started patients at 250 mg twice a day, or even 62.5 mg twice daily, especially in pediatric formulations or oral forms that include proguanil.

I also may begin with once-daily dosing and gradually increase based on patient tolerance. In many cases, lower doses are effective without needing to escalate.

Limitations of IV Therapy

Although intravenous ceftriaxone is sometimes used in Lyme disease treatment, I’ve not found it as helpful as I would like—particularly for patients with GI issues. Even though it bypasses the digestive tract initially, it still circulates back through the gut, potentially triggering the same symptoms.

Additionally, IV ceftriaxone is not the treatment of choice for common tick-borne co-infections like Babesia or Bartonella, limiting its utility in many cases.

Follow-Up and Monitoring

I routinely follow up with patients after one month of starting treatment. This helps me determine whether the lower dose is being tolerated, and whether it’s having a clinical benefit. If issues arise sooner, I encourage patients to contact me right away so we can make timely adjustments and avoid unnecessary suffering.

Final Thoughts: Individualized Care Matters

Lyme disease is a complex illness that often requires tailored treatment. Not everyone responds the same way to antibiotics—and some may not tolerate standard doses at all. That’s why a common-sense, compassionate approach to dosing is essential.

By adjusting medications to match each patient’s tolerance and clinical needs, we can often find a path forward—even when treatment seems daunting.