DDW 2011: Clostridium difficile Infection Risk Varies with Different Antibiotics

Increased risk of clostridium difficile infection may be associated with exposure to linezolid and clindamycin.

Although nearly half of all clostridium difficile infection (CDI) cases were unrelated to antibiotic exposure, higher CDI risk was associated with exposure to linezolid and clindamycin, according to an analysis of claims data from among 11.2 million commercially insured US individuals by Narayan Dharel, MD, a hospitalist at Beth Israel Deaconess Medical Center, Brockton, MA.

CDI is an important cause of morbidity and mortality among hospitalized patients, particularly among elderly and those who receive antimicrobial therapy, Dharel noted in a Digestive Disease Week 2011 poster presentation. Recently, increased incidences of CDI have been reported in populations previously thought to be at low risk, including healthy persons in the community. However, the status of CDI in the general US population and the associated risk factors remain largely unclear. The aim of Dharel’s analysis was to estimate the incidence of CDI in the general US population and to assess the risk associated with exposure to antibiotics in common use.

Dharel and colleagues identified 7,023 CDI cases over a 7.9 year period ending in 2007. Among these, investigators identified 3,527 cases of individuals who had been enrolled for at least two years prior to the onset of CDI. CDI was defined as any inpatient or outpatient claim coded as ICD-9 code 008.45 (International Classification of Diseases, 9th revision), or use of oral vancomycin to treat a presumptive CDI. These were compared with up to 10 controls matched on the basis of sex, age within two years, geographic region, type of insurer, subscriber status (individual, spouse or dependent), and date of enrollment within 1 year in a nested case-control study. Exposure to various antibiotics within the preceding 30, 60, and 90 days was evaluated using conditional logistic regression analyses.

Dharel found an average CDI incidence for the US population in this period of 16.4 cases per 100,000 person-years. He found also that CDI incidence increased exponentially from 0.3 per 100,000 person-years in 2000 to 39.7 per 100,000 person-years in 2006. In addition, not only did CDI risk increase with antibiotic use, it increased in relation to the number of antibiotics used. For patients receiving 1 antibiotic within the prior 30 days, the adjusted odds ratio was 5.83 (5.05-6.74, p<0.0001 versus none). For those receiving 3 or more, the odds ratio was 11.44 (8.27-15.84, p<0.0001 versus none).

Looking at antibiotic specific risk of CDI-exposure within 30 days, Dharel noted that risk was greatest among those individuals who had received linezolid (adjusted risk ratio [RR] 33.04; 95% confidence interval [CI] 5.38-202.83). Linezolid, an oral agent, Dharel commented, is commonly used in the community for MRSA and VRE infections. “People have to be aware of the increased risk,” he said. Risk was also raised with clindamycin (RR 14.9; 95% CI 10.8-20.6), fluoroquinolones (RR 6.43; 95% CI 5.43-7.6), and cephalosporins (RR 5.22; 95% CI 4.28-6.36). While macrolides had the lowest elevation in risk (RR 1.42; 95% CI 1.18-1.72), the increase for azithromycin was found to be nonsignificant (RR 1.11; 95 % CI 0.89-1.39). Of note, only 53% of the cases had a history of antimicrobial exposure within the preceding 90 days.

Dharel concluded, “CDI incidence is rapidly increasing in the US population. Antibiotic-associated CDI risk was highest with linezolid and clindamycin, and lowest with macrolides. Azithromycin conferred no significant risk.”

CDI infections flourish when antibiotics knock out normal gut flora, Dharel said in an interview. He noted that use of probiotics may be protective, and pointed out that CD spores are very resistant to chemical hand sanitizers. Hand washing is probably necessary for prophylaxis against contamination.

A search for other potential contributing factors is needed. Among them, may be changes in medication use in recent years, including increased use of proton pump inhibitors, cardiac medications, and chemotherapeutic agents.