What Drugs Cause Sepsis? Understanding Medication-Related Risk Factors

October 6, 2025 •

5 min read

Globally, sepsis impacts over 47 million people annually, and certain medications and illicit substances can be major contributing risk factors. While no drug directly causes the condition, they can compromise the immune system or act as a gateway for infection, which is the direct cause of sepsis. Understanding precisely what drugs cause sepsis is a critical step in managing risk.

Quick Summary

This article explores how different drug classes and illicit substances, such as immunosuppressants, chemotherapy, and opioids, can heighten the risk of developing sepsis. It details the mechanisms behind this increased risk, from immune system suppression to introducing pathogens through unhygienic practices. Specific examples are discussed along with vital prevention and risk reduction strategies.

Key Points

Immune Suppression: Medications like chemotherapy drugs and corticosteroids can significantly weaken the immune system, leaving individuals highly vulnerable to infections that lead to sepsis.
Intravenous Drug Use: The use of unsterile or shared needles introduces bacteria directly into the bloodstream, a major cause of infections like cellulitis and endocarditis that can progress to sepsis.
Opioid Effects: Opioid use can increase sepsis risk through immune modulation, gut microbiome dysbiosis, and the severe constipation that can lead to bacterial translocation.
Antibiotic Overuse: Paradoxically, the overuse or misuse of antibiotics can disrupt the body's protective microbiome, increasing the risk of subsequent, potentially drug-resistant infections that can trigger sepsis.
Early Recognition is Key: Timely recognition of infection and sepsis symptoms, such as fever, rapid heart rate, or confusion, is crucial for survival, especially in high-risk individuals.

Understanding the Mechanisms: How Drugs Increase Sepsis Risk

Sepsis is the body's life-threatening and overwhelming response to an infection. The infection-fighting processes turn on the body, leading to widespread inflammation, blood clots, and organ damage. While a drug itself does not directly trigger this cascade, certain pharmacological agents and substance use can create an environment where a simple infection can rapidly spiral into sepsis. The primary mechanisms involve suppressing the immune system and providing entry points for infection-causing pathogens.

Compromising the Immune System

Certain medications are designed to suppress the body's immune response, which can increase susceptibility to infections. If a patient on such medication develops an infection, their body is less equipped to fight it, increasing the risk of it progressing to sepsis.

Chemotherapy and Neutropenia: Cytotoxic chemotherapy agents, used to treat cancer, suppress bone marrow activity and can cause a predictable drop in neutrophil count, a condition known as neutropenia. Neutrophils are a type of white blood cell critical for fighting bacterial and fungal infections. When their numbers are critically low, a simple infection can become overwhelming, leading to neutropenic sepsis, a severe and life-threatening complication. The mortality rate for neutropenic sepsis can range from 2% to 21%.
Immunosuppressants: Used to treat autoimmune diseases (e.g., rheumatoid arthritis) and prevent organ transplant rejection, immunosuppressive drugs deliberately weaken the immune system. Examples include methotrexate, corticosteroids (like prednisone), and certain monoclonal antibodies (like rituximab). These agents significantly increase the risk of both bacterial and fungal infections that can lead to sepsis.
Psychotropic Agents: A class of drugs, particularly certain antipsychotics like clozapine, can, in rare cases, cause a severe form of neutropenia called agranulocytosis. This is a potentially fatal side effect where the body fails to produce enough neutrophils, leaving it highly vulnerable to infection and subsequent sepsis.

Promoting Infection and Microbiome Disruption

Beyond immune suppression, certain drugs create conditions that allow harmful pathogens to thrive or enter the body.

Intravenous (IV) Drug Use: Illicit drug use, particularly injecting drugs, is a major contributor to sepsis cases, even in otherwise healthy individuals. Repeated injection with contaminated or unsterile needles introduces bacteria (like Staphylococcus aureus) directly into the bloodstream. This can cause a range of serious infections that can quickly develop into sepsis, including cellulitis, abscesses, and endocarditis (an infection of the heart's inner lining). The opioid crisis has particularly highlighted the link between IV drug use and sepsis hospitalizations.
Opioid Abuse and the Gut: Chronic and high-dose opioid use, both prescribed and illicit, is associated with an increased risk of sepsis through other mechanisms as well. Opioids can cause severe constipation and bowel impaction. If left unresolved, this can lead to bacterial reabsorption from the intestines or, in extreme cases, perforation, allowing bacteria to spread into the body and trigger a systemic inflammatory response. Furthermore, chronic opioid treatment can cause gut microbiome dysbiosis, which impairs gut barrier integrity and allows bacterial translocation.
Antibiotics and Microbiome Disruption: In a counterintuitive manner, the overuse or inappropriate use of antibiotics can also increase the risk of sepsis. While essential for treating bacterial infections, antibiotics disrupt the body's natural microbiome, particularly in the gut. This disruption can make a patient more susceptible to new infections, sometimes caused by drug-resistant bacteria or Clostridium difficile. Research has shown that exposure to certain "high-risk" antibiotics is associated with a significantly increased risk of post-discharge sepsis.

Comparison of Sepsis Risk Factors Associated with Drug Types


Drug Type	Primary Mechanism for Increased Sepsis Risk	Examples of Associated Risks	Notes
Chemotherapy	Induces neutropenia, severely reducing the number of infection-fighting neutrophils.	Neutropenic sepsis from bacterial or fungal infections.	Predictable, dose-related risk. Requires proactive management during treatment.
Immunosuppressants	Deliberately suppresses the entire immune system.	Increased susceptibility to any bacterial, viral, or fungal infection.	Used for autoimmune diseases and transplant patients; close monitoring is essential.
Illicit IV Drugs	Introduces pathogens directly into the bloodstream via unsterile injection practices.	Cellulitis, abscesses, endocarditis, and other bloodstream infections.	High risk, often compounded by substance abuse and neglect of symptoms.
Opioids (Prescription & Illicit)	Immunosuppression, gut microbiome dysbiosis, and bowel impaction leading to bacterial translocation.	Increased infection risk, particularly pneumonia. Gut-derived sepsis.	Can suppress immune function and alter the gut barrier.
Antibiotics (Overuse)	Disrupts the body's protective microbiome, increasing susceptibility to new infections.	Infections from drug-resistant bacteria, C. difficile infection leading to sepsis.	A risk associated with antibiotic stewardship; longer duration increases risk.

Risk Reduction and Recognizing Warning Signs

For individuals on high-risk medications or with a history of substance abuse, proactive measures are essential. Prevention focuses on minimizing the risk of infection and being prepared to act quickly if symptoms arise. For hospitalized cancer patients, this often involves vigilant monitoring and aggressive treatment of any infection.

For patients on high-risk medications like chemotherapy or immunosuppressants:

Practice excellent personal hygiene, including frequent hand washing.
Avoid contact with sick individuals.
Promptly report any signs of infection, even mild ones, to your doctor.

For individuals who use intravenous drugs:

The safest option is to seek treatment for substance abuse.
If use continues, harm reduction strategies include using sterile syringes and clean water, and avoiding sharing equipment.
Never ignore signs of skin infection, such as redness, warmth, or swelling at injection sites.

Recognizing sepsis: Regardless of the underlying cause, early recognition and treatment are critical for survival. Be aware of signs and symptoms, especially if you or a loved one is at increased risk. These include fever, increased heart rate, rapid breathing, confusion, shivering, clammy skin, or extreme pain. If you have an infection and develop these symptoms, seek immediate medical attention and ask, "Could this be sepsis?".

Conclusion

While the concept that medications cause sepsis is a misnomer, understanding how certain drugs increase the underlying risk of infection is vital for prevention and patient safety. The pathways range from immune system suppression due to life-saving treatments like chemotherapy to compromised barriers and pathogen introduction related to substance abuse. For patients and healthcare providers, maintaining awareness of these risks and practicing vigilance in identifying and treating infections early is the most effective defense against this life-threatening condition. Knowing the factors involved helps equip everyone with the knowledge to reduce the risk and respond appropriately.

For more information on sepsis, visit the CDC website.

Frequently Asked Questions

No, an antibiotic does not directly cause sepsis. However, the misuse or overuse of antibiotics can disrupt your body's natural microbiome, increasing the risk of a new or drug-resistant infection, which could then lead to sepsis.

Chemotherapy drugs suppress bone marrow function, leading to a low white blood cell count (neutropenia). This weakens the immune system, making patients highly susceptible to infections that can easily progress to neutropenic sepsis.

Opioid use can increase sepsis risk in several ways: by suppressing the immune system, causing gut barrier dysfunction leading to bacterial translocation, or through the unhygienic practices of intravenous drug use that introduce bacteria into the bloodstream.

Yes, long-term use of corticosteroids is a risk factor for sepsis because these drugs are powerful immunosuppressants. They reduce the body's ability to fight off infections, making it easier for infections to progress to sepsis.

Injecting illicit drugs with unsterile or reused needles introduces bacteria directly into the bloodstream. This can lead to serious infections, like endocarditis (heart valve infection) or cellulitis, which can quickly trigger a systemic inflammatory response, leading to sepsis.

Yes, some other medications, though more rarely, can cause severe neutropenia, which increases sepsis risk. Examples include certain psychotropic drugs like clozapine and some antibiotics.

High-risk patients should be alert for any signs of infection, such as fever, chills, increased heart rate, rapid breathing, confusion, or a general feeling of being unwell. Promptly reporting any of these symptoms to a healthcare provider is critical for preventing sepsis.