Which antibiotic has the most serious side effects?

October 13, 2025 •

4 min read

Adverse drug events from antibiotics lead to an estimated 142,505 emergency department visits in the U.S. annually [1.8.2]. While life-saving, certain antibiotics carry a higher risk of severe side effects. So, which antibiotic has the most serious side effects?

Quick Summary

Several antibiotic classes are known for serious adverse effects. Fluoroquinolones can cause disabling, potentially permanent damage, while aminoglycosides are linked to hearing loss and kidney damage. This overview examines the high-risk antibiotics.

Key Points

Fluoroquinolones: This class carries FDA black box warnings for disabling and potentially permanent side effects, including tendon rupture and nerve damage [1.3.6].
Aminoglycosides: These are primarily associated with irreversible hearing loss (ototoxicity) and reversible kidney damage (nephrotoxicity) [1.4.1, 1.4.5].
Clindamycin: Clindamycin has one of the highest risks for causing severe and sometimes fatal Clostridioides difficile (C. diff) infection [1.6.2, 1.2.4].
Vancomycin: Requires careful monitoring to avoid kidney damage and hearing loss, and can cause a distinct infusion reaction known as vancomycin flushing syndrome [1.5.2, 1.5.4].
Linezolid: Associated with blood disorders (thrombocytopenia), nerve damage, and potentially fatal serotonin syndrome with prolonged use or drug interactions [1.7.3, 1.7.1].
Risk vs. Benefit: The use of any antibiotic, especially high-risk ones, requires a careful assessment by a clinician to weigh the benefits against the potential for serious harm [1.3.1].
Statistics: Adverse events from antibiotics are common, leading to over 140,000 emergency room visits annually in the U.S. [1.8.2].

Understanding Antibiotic Risks

Antibiotics are powerful medicines that fight bacterial infections, but they are not without risks. Adverse drug events (ADEs) are an underappreciated consequence of their use, with studies showing that roughly 20% of hospitalized patients receiving antibiotics experience an ADE [1.8.4, 1.8.6]. The most common side effects include gastrointestinal, kidney, and blood-related issues [1.8.4]. While many reactions are mild, some antibiotic classes are associated with severe, disabling, and even life-threatening side effects.

Fluoroquinolones: A High-Risk Class

Fluoroquinolones are a class of broad-spectrum antibiotics that includes drugs like ciprofloxacin (Cipro) and levofloxacin (Levaquin) [1.2.3]. The U.S. Food and Drug Administration (FDA) has issued multiple warnings, including a black box warning, due to their association with disabling and potentially permanent side effects [1.3.1, 1.3.6]. The risks are considered so significant that the FDA advises against their use for uncomplicated infections like sinusitis, bronchitis, and urinary tract infections when other options are available [1.3.1, 1.3.6].

Serious side effects associated with fluoroquinolones include:

Musculoskeletal System: Tendinitis and tendon rupture are among the most well-known risks. The Achilles tendon is commonly affected, but other tendons can be as well. The risk is higher in patients over 60, those with organ transplants, and those taking corticosteroid drugs [1.3.2, 1.3.6, 1.2.2].
Nervous System: These antibiotics can cause a range of neurological issues, including peripheral neuropathy (nerve damage in the arms and legs) that may be irreversible [1.3.6]. Central nervous system effects can include confusion, hallucinations, agitation, memory impairment, and delirium [1.3.3, 1.3.4].
Aortic Aneurysm and Dissection: The FDA has warned about an increased risk of ruptures or tears in the aorta, the body's main artery. This can lead to dangerous bleeding and death [1.3.4, 1.2.3]. Patients with a history of aneurysms, high blood pressure, or certain genetic disorders are at higher risk [1.2.3].
Mental Health Effects: Psychiatric adverse reactions such as depression, anxiety, paranoia, and even suicidal thoughts have been reported [1.3.4, 1.3.6].
Blood Sugar Disturbances: Fluoroquinolones can cause significant decreases in blood sugar (hypoglycemia), which can lead to a coma [1.3.6].

Aminoglycosides: Ototoxicity and Nephrotoxicity

Aminoglycosides, such as gentamicin and tobramycin, are potent antibiotics used for serious Gram-negative bacterial infections [1.4.1, 1.4.7]. Their use is limited by two major toxicities: ototoxicity (ear damage) and nephrotoxicity (kidney damage) [1.4.1, 1.4.5].

Ototoxicity (Hearing and Balance Damage): Aminoglycoside-induced ototoxicity is a significant concern, with reported incidences varying widely from 2% to 45% [1.4.1]. This damage can affect both hearing (cochleotoxicity) and balance (vestibulotoxicity) and is often irreversible [1.4.1, 1.4.6]. The drugs appear to generate free radicals in the inner ear, leading to the death of sensory hair cells [1.4.6]. Certain genetic mutations, such as in the MT-RNR1 gene, can dramatically increase a person's susceptibility to this hearing loss [1.4.4].
Nephrotoxicity (Kidney Damage): Kidney damage occurs in up to 10-25% of patients receiving aminoglycoside therapy [1.4.1]. The drug accumulates in the kidney's proximal tubular cells, causing damage that can lead to reduced kidney function [1.4.3]. Fortunately, this damage is generally reversible once the medication is stopped [1.4.1, 1.4.5].

Other High-Risk Antibiotics

While fluoroquinolones and aminoglycosides are often highlighted, other antibiotics also carry risks for serious side effects.

Clindamycin: This antibiotic is strongly associated with an increased risk of developing Clostridioides difficile infection (CDI) [1.2.4]. CDI is a severe form of diarrhea that can become life-threatening. Even a single dose of clindamycin can disrupt the gut microbiota so profoundly that it creates an environment for C. difficile to thrive [1.6.1, 1.6.2]. The risk for CDI with clindamycin is among the highest of all antibiotics [1.6.2, 1.6.3].
Vancomycin: Used to treat serious infections like MRSA, vancomycin can cause kidney damage (nephrotoxicity) and hearing loss (ototoxicity), particularly at high doses or in the elderly [1.5.2, 1.5.4]. It is also known for causing vancomycin flushing syndrome (formerly "red man syndrome"), an infusion-related reaction characterized by flushing and itching, if administered too quickly [1.5.2]. Severe skin reactions like Stevens-Johnson syndrome (SJS) are also a risk [1.5.2, 1.5.3].
Linezolid: This antibiotic can cause serious hematologic (blood-related) side effects like thrombocytopenia (low platelet count) with prolonged use [1.7.3, 1.2.2]. It is also associated with neuropathy (optic and peripheral) and a risk of serotonin syndrome when taken with certain other medications [1.7.1, 1.2.2]. Lactic acidosis, a dangerous buildup of lactic acid in the blood, is another rare but serious side effect [1.7.2, 1.7.4].

Comparison of High-Risk Antibiotics


Antibiotic Class	Primary Serious Side Effects	Key Considerations
Fluoroquinolones	Tendon rupture, permanent peripheral neuropathy, aortic aneurysm, central nervous system effects (hallucinations, confusion), psychiatric effects [1.3.1, 1.3.4, 1.3.6].	FDA advises restricting use for uncomplicated infections. Effects can be disabling and potentially irreversible [1.3.1].
Aminoglycosides	Irreversible hearing loss (ototoxicity), balance problems (vestibulotoxicity), reversible kidney damage (nephrotoxicity) [1.4.1, 1.4.5].	Dosing and patient monitoring are critical. Genetic factors can increase susceptibility to hearing loss [1.4.4].
Clindamycin	High risk of severe, potentially fatal Clostridioides difficile (C. diff) colitis [1.6.2, 1.6.5].	Disrupts gut flora significantly, even after a single dose. One of the highest CDI risks among all antibiotics [1.6.1, 1.6.2].
Vancomycin	Kidney damage, hearing loss, vancomycin flushing syndrome, severe skin reactions (SJS) [1.5.2, 1.5.4].	Requires blood level monitoring to balance efficacy and minimize toxicity [1.5.2].
Linezolid	Low blood platelets (thrombocytopenia), peripheral and optic neuropathy, serotonin syndrome, lactic acidosis [1.7.1, 1.7.3].	Risks increase with prolonged use. Numerous drug and food interactions (tyramine) [1.7.1, 1.7.6].

Conclusion

While no single antibiotic can be definitively named as having the absolute most serious side effects for every person, fluoroquinolones stand out due to the FDA's strong warnings about their potential for disabling and potentially permanent side effects affecting multiple body systems [1.3.1, 1.3.7]. Aminoglycosides also pose a significant threat due to the risk of irreversible hearing loss [1.4.5]. The risk profile of any antibiotic depends on the individual patient, including their age, kidney function, concurrent medications, and genetic predispositions [1.3.2, 1.4.1]. The decision to use a high-risk antibiotic always involves weighing the life-saving benefits against the potential for severe harm, a principle known as antibiotic stewardship.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional for diagnosis and treatment. For more information on antibiotic safety, you can visit the FDA's Drug Safety Communications.

Frequently Asked Questions

The FDA has issued black box warnings for fluoroquinolones due to their association with disabling and potentially permanent side effects, including tendinitis, tendon rupture, peripheral neuropathy, and central nervous system effects [1.3.1, 1.3.6].

Clindamycin is one of the antibiotics most strongly associated with causing Clostridioides difficile (C. diff) infection, a severe and potentially life-threatening form of diarrhea [1.2.4, 1.6.2].

Hearing loss caused by aminoglycoside antibiotics is often irreversible because the drug can cause permanent damage to the sensory cells in the inner ear [1.4.1, 1.4.5].

Vancomycin flushing syndrome (formerly red man syndrome) is an infusion-related reaction to vancomycin, characterized by itching and a rash on the face, neck, and upper body. It typically occurs when the antibiotic is administered too quickly [1.5.2].

Yes, elderly patients are often at higher risk for serious side effects from certain antibiotics, such as the risk of tendon rupture from fluoroquinolones and kidney or hearing damage from vancomycin and aminoglycosides [1.3.2, 1.5.4].

Peripheral neuropathy is damage to the nerves outside of the brain and spinal cord, which can cause weakness, numbness, and pain, usually in the hands and feet. Fluoroquinolones are known to cause this, and the damage can be permanent [1.3.6].

Linezolid is considered high-risk due to potential side effects with prolonged use, including blood disorders like low platelets (thrombocytopenia), nerve damage (optic and peripheral), and a risk of developing serotonin syndrome when combined with other drugs [1.7.3, 1.2.2].