Fever After Lyme Treatment in a Newborn: Sepsis or Herxheimer Reaction?
Quick Answer: Fever and clinical worsening after starting antibiotics in a newborn may signal sepsis—but in rare cases, it may be a Jarisch-Herxheimer reaction. Careful evaluation is critical.
Clinical Insight: The timing and progression of symptoms can help distinguish a Herxheimer reaction from sepsis—but infants must always be monitored closely.
When a 21-day-old infant developed fever and rapid heartbeat just hours after receiving antibiotics for Lyme disease, clinicians faced a critical question:
Was it sepsis—or something else?
This case highlights a rare but important phenomenon: a Herxheimer reaction can occur even in newborns—and may mimic a serious complication.
What Is a Herxheimer Reaction?
The Jarisch-Herxheimer reaction is a temporary inflammatory response that can occur after starting antibiotics for infections caused by spirochetes such as Borrelia burgdorferi, the bacterium responsible for Lyme disease.
It is thought to result from the release of bacterial components during treatment, triggering a surge in inflammatory cytokines.
Common symptoms include:
- Fever
- Tachycardia
- Irritability or decreased activity
- Worsening of existing symptoms
A Case of Herxheimer Reaction in a Newborn
A 21-day-old infant presented with:
- Poor feeding
- Decreased activity
- Abdominal distension
An erythema migrans rash was noted following a recent tick exposure, leading to a presumptive diagnosis of early Lyme disease.
Intravenous ceftriaxone was started.
Within two hours, the infant developed:
- Fever
- Tachycardia
- Clinical deterioration
These findings raised concern for sepsis—but were ultimately consistent with a Herxheimer reaction. :contentReference[oaicite:0]{index=0}
Herxheimer Reaction or Sepsis?
Fever after starting antibiotics in a newborn is a medical emergency until proven otherwise.
In infants, fever, rapid heart rate, and sudden clinical changes can raise immediate concern for sepsis—a potentially life-threatening condition requiring urgent evaluation.
However, a Jarisch-Herxheimer reaction can present in a similar way, with fever, tachycardia, and temporary worsening shortly after treatment begins.
The key distinction is timing and progression.
- Herxheimer reaction: Begins within hours of starting antibiotics and typically improves within 24 hours
- Sepsis: Often progresses without treatment and may worsen over time
Because missing sepsis can be dangerous, infants must always be carefully evaluated and monitored.
At the same time, clinicians should recognize that not all post-treatment deterioration represents infection.
Why Lyme Testing May Be Negative
In this case, Lyme testing was negative—a result that can be expected in early infection or in newborns whose immune systems are not fully developed.
Lyme disease in infants is often a clinical diagnosis, especially when an erythema migrans rash is present.
See more in our Lyme disease symptoms guide.
Recognizing Herxheimer Reactions in Infants
Although rare, Herxheimer reactions can occur in newborns and must be distinguished from more serious conditions.
Key considerations include:
- Timing shortly after antibiotic initiation
- Transient worsening rather than progression
- Resolution within hours to a day
Monitoring and supportive care are essential—but antibiotic therapy should not be stopped prematurely without careful evaluation.
The Science Behind the Reaction
The Herxheimer reaction is driven by an inflammatory response to bacterial die-off, involving cytokines such as TNF-alpha and interleukins.
In newborns, this response may appear sudden and severe—but is typically self-limited.
Clinical Takeaway
Fever after starting Lyme treatment in a newborn requires urgent evaluation for sepsis—but may, in rare cases, represent a Herxheimer reaction.
Recognizing the difference—while prioritizing safety—is critical to appropriate care.
References
Prodanuk M, et al. Lyme Disease in a Neonate Complicated by the Jarisch–Herxheimer Reaction. Pediatric Infectious Disease Journal, 2020.
Nykytyuk O, et al. Insights into the Pathophysiology of the Jarisch-Herxheimer Reaction. Infect Dis Rev, 2020.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
