Study Finds Certain Antibiotics Linked to Increased Mortality Rate and Organ Dysfunction

Side effects of antibiotics like Zosyn were linked to more deaths among patients, leading researchers to question the use of antianaerobic antibiotics for sepsis.

The findings of a new study suggest that side effects of certain antibiotics used to treat sepsis may actually increase the risk of death and interfere with organ functions.

Researchers from the University of Michigan warn that they found higher mortality rates among patients treated with vancomycin and piperacillin-tazobactam, compared to those treated with vancomycin and cefepime, in a report published this week in the medical journal JAMA Internal Medicine, concluding that the use of broad-spectrum antianaerobic antibiotics for sepsis treatment might cause unnecessary harm.

Vancomycin and piperacillin-tazobactam are antibiotics used to treat bacterial infections. Vancomycin targets gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and is used for serious infections when other antibiotics fail. Piperacillin-tazobactam, sometimes sold under the brand name Zosyn, combines piperacillin, which disrupts bacterial cell walls, with tazobactam, which prevents bacterial resistance.

Both antibiotics are commonly used in hospitals to treat severe infections like sepsis, which is a life-threatening condition that occurs when an individual’s immune system has a dangerous response to an infection and starts to damage the body’s tissues and organs. Symptoms of sepsis include decreased blood pressure, increased heart rate, fever, confusion, shortness of breath, weakness, and can result in organ failure or death.

In this latest study, researchers analyzed 7,569 sepsis patients during a 15-month piperacillin-tazobactam shortage. The study aimed to compare 90-day mortality rates in sepsis patients treated with either piperacillin-tazobactam or cefepime.

The retrospective cohort study analyzed hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including the shortage period from June 12, 2015, to September 18, 2016. Researchers included data on adult patients suspected of having sepsis who were treated with vancomycin and either piperacillin-tazobactam or cefepime, where both treatments were deemed equally suitable.

Researchers looked for data on 90-day mortality, with secondary outcomes measuring days free from organ failure, ventilator use, and vasopressor use.

According to the findings, 4,523 received vancomycin and piperacillin-tazobactam, while 3,046 were treated with vancomycin and cefepime. A small number (3%) received piperacillin-tazobactam during the shortage. The analysis found that piperacillin-tazobactam was linked to a 5% increase in 90-day mortality and 2.1 fewer organ failure–free days, 1.1 fewer ventilator-free days and 1.5 fewer vasopressor-free days.

“Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime,” the researchers determined. “These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.”