Can Ceftriaxone Cause Drug Fever? Understanding the Risks

October 12, 2025 •

3 min read

While drug-induced fever is an uncommon side effect, it is estimated to occur in 3-5% of adverse drug reactions requiring hospitalization [1.4.4]. As a beta-lactam antibiotic, questions often arise about its potential to cause this reaction, so can ceftriaxone cause drug fever?

Quick Summary

Ceftriaxone, a widely used beta-lactam antibiotic, can indeed cause drug fever, though it is considered a rare side effect. This reaction typically occurs 7-10 days after starting the medication.

Key Points

Ceftriaxone Can Cause Fever: Ceftriaxone, a beta-lactam antibiotic, is known to cause drug fever, although it's a rare side effect (less than 0.1% incidence) [1.2.6].
Typical Onset: Drug fever from antibiotics like ceftriaxone typically appears 7 to 10 days after starting treatment, but the timing can vary [1.6.2].
Mechanism is Often Hypersensitivity: The fever is usually caused by a hypersensitivity or idiosyncratic reaction, where the body's immune system reacts to the drug [1.4.1, 1.6.5].
Diagnosis by Elimination: Diagnosis involves ruling out other causes of fever and observing that the fever subsides after stopping the medication [1.4.6].
Management is Discontinuation: The primary treatment is to stop taking ceftriaxone, with the fever usually resolving within 48-72 hours [1.6.2].
Beta-Lactams are a Common Cause: The class of antibiotics that includes ceftriaxone (beta-lactams) is one of the most frequently implicated drug classes in causing drug fever [1.4.4].
Symptoms: Besides fever, other signs like rash or eosinophilia may be present, but often the patient feels relatively well despite a high temperature [1.3.4, 1.6.1].

Understanding Ceftriaxone and Its Role

Ceftriaxone is a third-generation cephalosporin antibiotic used to treat a wide variety of bacterial infections [1.5.9]. It works by inhibiting the synthesis of the bacterial cell wall, leading to the death of the bacteria [1.2.7]. It is administered via intramuscular or intravenous injection and is effective against infections like pneumonia, meningitis, skin infections, and gonorrhea [1.5.6, 1.5.7]. While generally well-tolerated, like all medications, it carries a risk of side effects, including the potential for drug-induced fever [1.2.6, 1.5.5].

What is Drug Fever?

Drug fever is a febrile response to a medication, where the fever is not caused by the underlying illness or another source of infection [1.3.9]. The diagnosis is often one of exclusion, confirmed when the fever resolves after discontinuing the suspected medication [1.4.6]. The onset of drug fever is typically 7 to 10 days after initiating the drug but can vary from hours to weeks [1.6.1, 1.6.2]. A key characteristic is that patients often feel surprisingly well despite having a high temperature, which can range from 102°F to 104°F (38.8°C to 40°C) [1.6.1].

Can Ceftriaxone Cause Drug Fever?

Yes, ceftriaxone can cause drug fever [1.2.6, 1.5.5]. It is listed as a rare side effect, occurring in less than 0.1% of patients [1.2.6]. Beta-lactam antibiotics, the class to which ceftriaxone belongs, are one of the most common groups of drugs associated with drug fever [1.4.4, 1.4.6]. The reaction is often part of a hypersensitivity or idiosyncratic response [1.2.2, 1.6.5].

The median time to the onset of fever after starting an antimicrobial is about 6 days [1.6.1]. For ceftriaxone specifically, the onset can vary. In some cases, a fever and other symptoms have appeared days after the treatment course has finished [1.6.3, 1.6.4]. The fever pattern can be continuous (not varying) or intermittent (with normal temperatures in between) [1.3.4].

Mechanisms of Ceftriaxone-Induced Fever

Several mechanisms can lead to drug fever, and the exact process for ceftriaxone is often considered idiosyncratic or related to a hypersensitivity reaction [1.6.5].

Hypersensitivity Reaction: This is the most common cause. The drug, or a metabolite, acts as an antigen, triggering an immune response that leads to the release of pyrogens (fever-inducing substances) [1.4.1]. This can sometimes be accompanied by other signs like a rash or eosinophilia (an increase in a type of white blood cell) [1.3.4, 1.4.6].
Idiosyncratic Reaction: This type of reaction is unpredictable and not related to the drug's known pharmacological effects. It may be due to a patient's genetic predisposition that affects how their body processes the drug [1.2.2, 1.6.5].
Jarisch-Herxheimer Reaction: Though different from classic drug fever, this reaction can occur when antibiotics like ceftriaxone are used to treat spirochetal infections (e.g., syphilis, Lyme disease). The rapid killing of bacteria releases a large amount of endotoxins, causing a systemic inflammatory response that includes fever, chills, and worsened symptoms [1.2.2, 1.6.8].

Diagnosis and Management

Diagnosing ceftriaxone-induced drug fever involves a process of elimination [1.4.6]. A healthcare provider must first rule out other causes of fever, such as the initial infection not responding to treatment, a new secondary infection, or other inflammatory conditions [1.3.9]. A key indicator is the timing of the fever in relation to starting the drug and the absence of other symptoms that would point to a different cause [1.4.6].

The definitive step in both diagnosis and management is to discontinue the suspected medication [1.4.6]. If ceftriaxone is the cause, the fever typically resolves within 48 to 72 hours of stopping the drug [1.6.2]. A drug re-challenge (re-administering the drug) is not usually recommended but, when performed, results in a recurrence of symptoms, confirming the diagnosis [1.3.4]. If the antibiotic is still needed, a healthcare provider will switch to a different class of antibiotics that is less likely to cause a similar reaction [1.4.6].

Comparison of Drugs Causing Fever

Many medications can cause drug fever. Here is a comparison of some common classes.


Drug Class	Common Examples	Typical Onset Mechanism
Antimicrobials	Beta-lactams (Penicillin, Ceftriaxone), Sulfonamides, Vancomycin	Hypersensitivity [1.4.1, 1.4.4]
Anticonvulsants	Phenytoin, Carbamazepine	Hypersensitivity [1.4.1, 1.4.3]
Cardiovascular Drugs	Procainamide, Quinidine, Methyldopa	Hypersensitivity or Pharmacologic Action [1.4.3, 1.4.6]
Antineoplastic Agents	Bleomycin, Interferons	Direct Pharmacologic Action, Release of Pyrogens [1.4.1, 1.4.4]
CNS Drugs	Anticholinergics, Amphetamines	Altered Thermoregulation [1.4.1]

Conclusion

While it is a rare event, ceftriaxone can cause drug fever, typically as part of a hypersensitivity or idiosyncratic reaction [1.2.6, 1.6.5]. The reaction usually develops about a week into therapy and resolves within a few days of stopping the medication [1.6.1, 1.6.2]. It is crucial for both patients and clinicians to be aware of this potential side effect. If an unexplained fever develops during or after a course of ceftriaxone, it should be discussed with a healthcare provider immediately to determine the cause and appropriate course of action.

For more information from an authoritative source, you can visit MedlinePlus's page on Ceftriaxone Injection. [1.2.4]

Frequently Asked Questions

Drug fever from ceftriaxone is considered rare, with a reported incidence of less than 0.1% [1.2.6].

The average onset for antibiotic-induced drug fever is 7-10 days after starting the medication, though it can range from a few hours to several days or more [1.6.2].

If you experience a fever while on ceftriaxone, you should call your doctor immediately. It could be a sign of a drug reaction, a worsening infection, or another serious side effect [1.3.1, 1.5.2].

The main treatment is to discontinue the ceftriaxone. The fever typically resolves on its own within 48 to 72 hours after stopping the drug [1.6.2].

Yes, while sometimes fever is the only symptom, other signs can include rash, chills, and elevated white blood cell counts (eosinophilia) [1.3.4]. In more severe cases, like DRESS syndrome, there can be systemic involvement [1.2.3].

Often, yes. Drug fever is frequently a manifestation of a drug hypersensitivity reaction, where the immune system responds to the medication [1.4.1].

You should discuss this with your doctor. There can be cross-sensitivity between different cephalosporin antibiotics and penicillins, so your doctor will need to determine the safest alternative [1.5.5].