Using drug stewardship to reduce C. diff

AHRQ toolkit can guide the process

Antimicrobial stewardship programs specifically targeting Clostridium difficile infections offer a promising path to protect patients from this enteric scourge, but may have little effect unless a broad range of other infection control measures are also put in place, researchers are finding.

To help infection preventionists consider if antibiotic prescribing patterns are contributing to their C. diff infection rates, the Agency for Healthcare Research and Quality (AHRQ) has created a toolkit outlining how to use ASP to reduce C. diff infections. (Available on line at: For example, reducing inappropriate use of broad spectrum antibiotics like the fluoroquinolones — a worthy goal regardless of other factors — may thwart the emergence of C. diff in the patient’s gut.

“Antibiotics may kill off some of the ‘good’ bacteria that protects us and basically oppose C. diff,” says Belinda Ostrowsky, MD, MPH, principal clinical investigator for the AHRQ toolkit project and director of the antimicrobial stewardship program at the Montefiore Medical Center in New York City. “The fluoroquinolones in particular have been associated with many outbreaks of this very virulent NAP1 C. diff strain. That strain seems to have more resistance to the quinolones.”

Indeed, the emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain around the turn of this century has driven a C. diff epidemic that now claims some 14,000 lives annually in the U.S. From 2000 to 2009, the number of hospitalized patients with any C. diff discharge diagnoses more than doubled, from approximately 139,000 to 336,600, and the number with a primary C. diff diagnosis more than tripled, from 33,000 to 111,000, the Centers for Disease Control and Prevention reports.1

Common sequelae include diarrhea, colitis, toxic megacolon, sepsis, and death. NAP1 has become the predominant outbreak strain of C. diff via several selective advantages that include enhanced spore formation, a 20-fold increase in toxins, a lower infectious dose, and the ability to survive indefinitely in the environment. As with any strain of C. diff, the spores are difficult to remove from the hands and switching from alcohol rubs to soap and water hand washing is generally recommended during an outbreak.

C. diff is complicated,” Ostrowsky says. “First, it depends how you think somebody really got C. diff. Was it passed between patients on health care worker hands? Maybe the environment wasn’t cleaned properly. Or is it that someone basically gets too many antibiotics, their flora changes and they suddenly have ‘unopposed’ bacteria and then they get C. diff. The truth is it is probably a combination of all of those things.”

Thus an antibiotic stewardship program in the absence of other interventions is unlikely to be effective. The 10 hospitals participating in the AHRQ ASP project also had measures in place like immediate patient isolation with onset of diarrhea without waiting for laboratory confirmation of C. diff, contact precautions including use of gowns and gloves and strict hand washing with soap and water if possible, and stringent surface disinfection policies. The AHRQ program builds on a general antimicrobial stewardship toolkit developed by the Greater New York Hospital Association/United Hospital Fund. The toolkit helps individual hospitals identify antibiotics most linked to C. diff infections at their hospital so they know which ones to target. The toolkit then guides hospitals in development of strategies to improve appropriate use of antibiotics.

IPs key team members

As a starting point, the AHRQ toolkit assumes that your hospital already has an ASP which can be tailored to specific measures to reduce antibiotics associated with C. diff. Implementing and maintaining an effective ASP requires a dedicated multidisciplinary team and ongoing communication and collaboration as well as ongoing monitoring of systems. Team membership will vary among organizations, but the core team should include an infectious disease physician, a pharmacist, clinical microbiologist, infection preventionist, hospital epidemiologist, information technology (IT) representative, and a senior administrator. Ideally, the team should be supported by an in-house lab and IT resources, AHRQ recommends.

The toolkit describes an individualized approach and tailoring of selected stewardship interventions based on the results of limited case-control studies or risk assessments at each facility.

“When we did our limited case control study the quinolones came up high on the list in association with C. diff,” Ostrowsky says. “For that drug we made some changes in our restriction policies. To do that, we actually loosened up restrictions on a different antibiotic to try to steer people away from the quinolones. We also put some education in place to try to get people away from [prescribing] that class of drugs.”

Another drug that was linked to C. diff at Montefiore is the broad spectrum antibiotic piperacillin/tazobactam, which was often the choice for empiric therapy when nursing home patients were admitted to the hospital, she adds. The identified problem was the long duration of antimicrobial therapy in some patients, so Ostrowsky and colleagues set up an “audit feedback” program to prompt providers to consider a more narrow spectrum drug rather than continue the piperacillin/tazobactam.

All of the AHRQ project hospitals that put in place elements of the antibiotic stewardship program directed at C. diff decreased use of at least one targeted antibiotic associated with the infection, she notes. That said, reducing C. diff infection rates through this method may take time, as the 10 hospitals had mixed overall results in terms of actually reducing infections.

“It may be that you need to get more of your antibiotic burden down, but it probably translates into better care for the patient even if I can’t measure that in an overall rate of C. diff that goes down,” she says. “I’m still optimistic even if we are not able to prove it all with one study — it takes time to get things in place. The places that had these interventions in place actually got a lot of recognition from their providers. Once you get the providers on board — a key part of the tool kit is getting physician champions behind you. Because they need to recognize that there is a problem in order to be able to help you fix it.”


  1. CDC. Vital Signs: Preventing Clostridium difficile Infections. MMWR 2012;61(09):157-162