various blister packs of medication antibiotics
Julie Hambleton
Julie Hambleton
May 25, 2024 ·  4 min read

Some Common Antibiotics May Cause More Harm Than Good In Sickest Patients

Antibiotics are widely used to treat bacterial infections and are often considered lifesaving medications. However, a recent study suggests that some commonly used antibiotics may have unintended consequences, particularly in the sickest patients. The study, conducted by Robert Dickson, M.D., and his team, investigated the differences in patient mortality between the usage of two antibiotics: piperacillin/tazobactam and cefepime. This research highlights the need for careful consideration when prescribing antibiotics for critically ill patients.

Potentially Dangerous Antibiotics: The Study

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The discovery of the potential harm of a common antibiotic used in the hospital setting was truly more by chance and circumstance than innate curiosity. The study was prompted by a 15-month national shortage of piperacillin/tazobactam, commonly known as Zosyn, beginning in 2015. This antibiotic is frequently used to treat sepsis in hospitals. While incredibly effective against sepsis bacteria, it simultaneously destroys all gut bacteria, as well. In the absence of Zosyn, clinicians turned to cefepime, an alternative with similar activity against common sepsis pathogens but minimal effects on anaerobic gut bacteria. This shortage provided an opportunity to analyze the differences in patient outcomes between the two antibiotics. (1)

Read More: Can You Treat UTIs Without Antibiotics?

The Findings

The rise of antibiotic-resistant bacterial infections. Super bugs. A microbiological culture Petri dish with bacteria and an antibiotic resistance test
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Initially, there were no significant differences in patient outcomes when comparing the short-term effects of the two antibiotics. However, three months later, the study revealed that patients treated with piperacillin/tazobactam had a 5% increase in 90-day mortality. These patients also spent more time on ventilators and experienced more organ failure. This suggests that the choice of antibiotic can influence long-term outcomes in critically ill individuals. (2)

“We saw this Zosyn shortage as a one-of-a-kind opportunity to ask whether this antibiotic, which we know depletes the gut of anaerobic bacteria, makes a difference in terms of patient outcomes,” said Robert Dickson, M.D. of the Department of Medicine’s Division of Pulmonary & Critical Care Medicine and Deputy Director of the Weil Institute for Critical Care Research & Innovation. (3)

Understanding Sepsis and the Role of Antibiotics

Patient laying on patient's bed in hospital, patient receive saline solution to treat illness.
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Sepsis is a life-threatening condition caused by the body’s response to an infection. It occurs when the immune system overreacts, leading to widespread inflammation and organ dysfunction. Antibiotics play a crucial role in treating sepsis because they target the underlying bacterial infection that triggers the condition. Prompt administration of appropriate antibiotics can significantly improve patient outcomes and reduce mortality rates. (4)

Exploring the Gut Microbiome

Intestine in hands. Microbiome of digestive system. Probiotic treatment. Probiotic cells for immunity. Digestive health. Studying action of probiotics. Microflora of intestinal tract
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The gut microbiome refers to the complex ecosystem of bacteria residing in the human gastrointestinal tract. These bacteria play a vital role in maintaining overall health, aiding digestion, synthesizing essential nutrients, and supporting the immune system. However, the gut microbiome is susceptible to disruption by various factors, including antibiotics. (5)

Antibiotics are designed to eliminate bacteria, including those causing infections. However, they can also inadvertently affect the beneficial bacteria in the gut. This disruption can lead to an imbalance in the microbiome, potentially compromising its beneficial functions. The overuse or misuse of antibiotics can disrupt the delicate balance, causing long-term consequences, such as increased susceptibility to infections and other health issues.

Read More: Antibiotics Can Destroy Good Bacteria and Permanently Slow Your Child’s Metabolism

The Implications of the Study

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The findings of the study hold significant implications for clinical practice. With sepsis being a prevalent condition, the choice of antibiotic for the sickest patients becomes crucial in determining their outcomes. The observed 5% increase in 90-day mortality associated with piperacillin/tazobactam highlights the need for cautious consideration in antibiotic selection.

“These are powerful antibiotics that are administered to patients every day in every hospital nationwide,” said Rishi Chanderraj, M.D. of the Division of Infectious Disease. “Clinicians use them because they are trying to treat every possible pathogen that might be causing their patients’ illness. But our results suggest that their effects on the microbiome might also have important effects on patient outcomes.”

Dr. Dickson agrees: “A 5% mortality difference has enormous implications because sepsis is so common. Every day, thousands of clinicians are deciding which of these drugs to use in septic patients.”

Dr. Dickson and Dr. Chanderraj emphasize the importance of viewing antibiotics in a similar light as chemotherapy. While they can be life-saving in the right context, they can also pose risks if used inappropriately. Decisions regarding antibiotic use should be based on careful assessment of individual patient needs, considering both the potential benefits and harms.

The Bottom Line

close up pharmaceuticals antibiotics pills medicine in blister packs. colorful antibacterials pills Pharmacy background. capsule pill medicine Antimicrobial drug resistance. Pharmaceutical industry
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The study reveals that some commonly used antibiotics, such as piperacillin/tazobactam, may have detrimental effects in the sickest patients. This reinforces the need for ongoing research and better understanding of antibiotic therapy in critical care settings. Healthcare professionals must strive to strike the right balance between the benefits and potential harm of antibiotic use. By doing so, they can ensure the best possible outcomes for patients battling severe infections, such as sepsis.

Read More: 7 of Nature’s Most Powerful Antibiotics


  1. Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime.” JAMA Network. Rishi Chanderraj, MD, MSc. May 13, 2024.
  2. Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute InfectionThe ACORN Randomized Clinical Trial.” JAMA Network. Edward T. Qian, MD, MSc. October 14, 2023.
  3. Commonly used antibiotic brings more complications, death in the sickest patients.” Medical Express. May 2024.
  4. What is Sepsis?” Sepsis
  5. Gut Microbiome.” Cleveland Clinic