New study: Sepsis care initiatives may lead to higher C. difficile infection rates, antibiotic resistance


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Liz Garman


New study: Sepsis care initiatives may lead to higher C. difficile infection rates, antibiotic resistance
For the first time, research Identifies consequences of integrated sepsis screening & treatment

Arlington, Va., October 3, 2017–Healthcare experts have long known the benefits of integrated sepsis care programs, yet less information has been published on potential unintended consequences of these programs.  

That’s changed with a new study that suggests that electronic sepsis screenings and treatment protocols could, in fact, lead to increased use of certain broad-spectrum antibiotics and healthcare facility-onset (HCFO) C. difficile infection (CDI) rates, according to findings published in the October issue of the American Journal of Infection Control (AJIC), the journal of the Association for Professionals in Infection Control and Epidemiology (APIC).

The research is the first to address the inadvertent impact of sepsis care programs on broad-spectrum antibiotic use among hospitals and nursing unit-levels—and follows previous reports demonstrating the effectiveness of sepsis care programs, now a part of most hospitals.

Lead researcher Jashvant Poeran, MD, PhD, Assistant Professor of Population Health Science and Policy, Orthopaedics, and Medicine at the Icahn School of Medicine at Mount Sinai, alongside colleagues from The Mount Sinai Hospital, analyzed adult inpatients at a 1,171-bed tertiary care teaching hospital who were admitted to nursing units with both sepsis care bundle programs in place and the highest incidences of sepsis, antibiotic use, and HCFO CDI. Researchers collected data on the administration of broad-spectrum antibiotics per 1,000 patient days and HCFO CDI data per 10,000 patient days from June 2011 through July 2014.

Poeran and his team defined sepsis care bundle programs as sepsis screenings integrated into a hospital’s electronic health record and EHR-triggered antibiotic administration. This protocol aims to standardize initial evaluation and subsequent sepsis management orders, including monitoring, laboratory tests and fluid and antibiotic administration. The order set recommends broad-spectrum antibiotics available for use without preauthorization from a hospital’s antibiotic stewardship team. These broad-spectrum antibiotics can increase the risk of CDI.

Among the findings: 

  • Over 127,346 total patient days, researchers recorded increased antibiotic use and HCFO CDI during sepsis care bundle implementation, with the period directly following the implementation phase accounting for the highest rate of antibiotic use (50.4 days of therapy [DOT] per 1,000 patient days).
  • Specifically, while HCFO CDI rates were decreasing before sepsis care bundle implementation (-1.4 events per 10,000 patient days/month) they began to increase during (1.6 events per 10,000 patient days/month) and following (10.8 events per 10,000 patient days/month) implementation.
  • Over the three-year timeframe, the data recorded an HCFO CDI rate of 14.4 per 10,000 patient days/month.
  • While overall, cefepime was the most commonly used antibiotic, the main driver of increased antibiotic use was levofloxacin which, interestingly, was not part of the sepsis care order set. In the period directly following sepsis care bundle implementation phase (compared to the period before implementation) levofloxacin increased by 32.7 DOT per 1,000 patient days.
  • Researchers proposed several explanations for the study’s findings. For one, the increase in antibiotic administration could mirror the general increase in sepsis cases. But, as the study’s authors write, the uptick could also be due to changes in documentation and diagnosis patterns. Integrated sepsis care programs may identify septic patients earlier in their disease course. This would lead to increased doses of antibiotics, particularly if antibiotics can be prescribed without preauthorization.

“Integrated sepsis care streamlines how treatment is delivered. Yet as our research indicates, providers face the tough task of addressing how to deliver timely sepsis care, while mitigating potential unintended consequences such as an increase in healthcare facility-onset Clostridium difficile infection that may be linked to increased use of broad-spectrum antibiotics,” said Dr. Poeran, the study’s lead researcher and an Assistant Professor at the Icahn School of Medicine at Mount Sinai. “Hospitals’ antibiotic stewardship teams can use these observations to align protocol with processes that ensure appropriate antibiotic administration.”

“Routine integrated sepsis treatment remains an integral part of how providers deliver rapid care to counter a sepsis diagnosis,” said Linda Greene, RN, MPS, CIC, FAPIC, 2017 APIC president. “But this is a double-edged sword: How do we prevent and treat sepsis while minimizing antibiotic resistance? We cannot diminish the importance of implementing swift treatment, but so, too, do we need more research to uncover solutions to the unintended consequences that ensue.”

Sepsis remains the leading cause of death in U.S. hospitals. Across the country, a person receives a sepsis diagnosis every 20 seconds, accounting for 1.6 million people in the U.S. per year. Some 258,000 people die from the disease. That’s one sepsis-related death every two minutes.

Visit to learn more information about preventing infections in healthcare facilities.

AJIC ( covers key topics and issues in infection control and epidemiology. Infection preventionists, including physicians, nurses, and epidemiologists, rely on AJIC for peer-reviewed articles covering clinical topics as well as original research. As the official publication of APIC, AJIC is the foremost resource on infection control, epidemiology, infectious diseases, quality management, occupational health, and disease prevention. AJIC also publishes infection control guidelines from APIC and the CDC. Published by Elsevier, AJIC is included in MEDLINE and CINAHL.

APIC’s mission is to create a safer world through prevention of infection. The association’s more than 15,000 members direct infection prevention programs that save lives and improve the bottom line for hospitals and other healthcare facilities. APIC advances its mission through patient safety, implementation science, competencies and certification, advocacy, and data standardization. Visit APIC online at Follow APIC on Twitter: and Facebook: For information on what patients and families can do, visit APIC’s Infection Prevention and You website at

Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates,” by Robert Hiensch, Jashvant Poeran, Patricia Saunders-Hao, Victoria Adams, Charles A. Powell, Allison Glasser, Madhu Mazumdar and Gopi Patel, appears in the American Journal of Infection Control, Volume 45, Issue 10 (October 2017).


Robert Hiensch, MD (Corresponding author)
Assistant Professor, Medicine, Pulmonary, Critical Care and Sleep Medicine
Icahn School of Medicine at Mount Sinai

Jashvant Poeran, MD, PhD
Assistant Professor, Population Health Science and Policy; Medicine; Orthopaedics
Icahn School of Medicine at Mount Sinai

Patricia Saunders-Hao, PharmD, BCPS
Clinical Pharmacy Specialist
The Mount Sinai Hospital 

Victoria Adams, PharmD
Clinical Pharmacy Specialist
Johns Hopkins Bayview Medical Center

Charles A. Powell, MD
Director, Mount Sinai-National Jewish Health Respiratory Institute 
Professor, Medicine, Pulmonary, Critical Care, and Sleep Medicine
Icahn School of Medicine at Mount Sinai

Allison Glasser
Senior Director, Clinical Excellence
ffice of the Chief Medical Officer
Mount Sinai Health System 

Madhu Mazumdar, PhD
Director, Institute for Health Care Delivery Science
Professor, Population Health Science and Policy; Orthopaedics
Icahn School of Medicine at Mount Sinai 

Gopi Patel, MD
Associate Professor, Medicine, Infectious Diseases
Icahn School of Medicine at Mount Sinai

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