Incidence of Clostridium difficile Infections in Patients Receiving Antimicrobial and Acid-suppression Therapy

Rachel N. King, Pharm.D.; Stephanie L. Lager, Pharm.D.

Disclosures

Pharmacotherapy. 2011;31(7):642-648. 

In This Article

Abstract and Introduction

Abstract

Study Objectives. To determine the incidence of Clostridium difficile infection (CDI) at one community hospital by identifying patients with stool samples positive for. C. difficile toxin A or B, and to compare the incidence with a 2008 national estimate; and to determine which patient characteristics and concomitant antimicrobial and acid-suppression drugs are risk factors for the development of CDI.
Design. Retrospective, single-center, medical record review.
Setting. 350-bed community hospital.
Patients. A total of 11,010 admissions between January 1, 2009, and December31, 2009; 115 of these patients had stool samples positive for C. difficile toxin A or B.
Measurements and Main Results. All C. difficile toxin A and B enzyme immunoassay tests were performed by a central laboratory. The incidence of CDI was 10.4 cases/1000 patient admissions, which was significantly lower than the overall incidence reported in a 2008 national survey of 13.1 CDI cases/1000 patient admissions (p=0.021). Demographic and clinical data of the patients with CDI were collected by using electronic medical records. Patients were more likely to be elderly and female, and to have developed CDI during hospitalization. Of the 115 patients, 95 (82.6%) received acid-suppression therapy and 91 (79.1%) received antimicrobials. Of the patients receiving acid-suppression therapy, 72 (75.8%) received a proton pump inhibitor during their hospitalization, and 49 (51.6%) received both a proton pump inhibitor and an antibiotic. The most frequently used antibiotics in this population were fluoroquinolones, cephalosporins, and carbapenems, with a significantly larger proportion of patients who received carbapenems developing CDI compared with the other classes of antibiotics (p<0.05 for both comparisons). Patients receiving antimicrobial and acid-suppression therapy were more likely to develop CDI than those who did not receive these drugs.
Conclusion. The incidence of CDI in 2009 at one community hospital was significantly lower than a 2008 national estimate. Antimicrobial and acid-suppression therapies—in particular, combinations of fluoroquinolones, cephalosporins, carbapenems, and proton pump inhibitors—were found to be risk factors for the development of CDIs in hospitalized patients.

Introduction

Clostridium difficile is the most common cause of nosocomial diarrhea and has become a major problem in health care facilities in the United States.[1–8] There are many nonmodifiable host characteristics that place patients at risk for contracting C. difficile infection (CDI). These include advanced age, female sex, prolonged hospital length of stay, and comorbid diseases.[1,2,5] There are also modifiable risk factors that provide areas for pharmacist intervention, specifically antimicrobial stewardship and appropriate prescribing of acid-suppression drugs. Prolonged exposure to antibiotics and treatment with mul-tiple antibiotics suppress the normal gastro-intestinal flora, allowing C. difficile to cause infection.[1–3,5,7,9] Recent studies have shown that β-lactams, clindamycin, and fluoroquinolones are the antibiotics most commonly associated with the development of CDI.[2,5,6] Acid-suppression therapy is also a controversial topic in the development of CDI.[10–12] Gastric acid production, which is the body's natural defense against the ingestion of C. difficile spores, is decreased, leaving the patient vulnerable to acquiring CDI.[10–13] Current practice guidelines mention a possibility that proton pump inhibitors and histamine2 (H2)-receptor antagonists can be associated with CDI, although the role of both proton pump inhibitors and H2-antagonists in the development of CDI remains unclear.[1]

Although CDI is not a reportable condition in the United States,[1] studies have suggested an increasing prevalence of CDI.[7] International Classification of Diseases, Ninth Revision codes were analyzed from patients in the National Hospital Discharge Survey.[14] The results showed that CDI rates had almost doubled between 1996 and 2003 from 31 to 61 cases/100,000 population. Another survey estimated a doubling of CDI rates between 1999 and 2005, from 37.6 to 76.9 episodes/10,000 discharges.[15] Although this information is helpful in determining the prevalence of CDI, it is not an overall estimate of CDI rates in the United States.

A survey conducted in 2008 by the Association for Professionals in Infection Control and Epidemiology Incorporated (APIC) provides a more accurate estimate of national CDI rates.[7] The survey included 12.5% of all U.S. acute care facilities. Their results showed an overall incidence of 13.1 cases of CDI/1000 inpatients. Of these patients, most were women and older than 60 years. Health care–associated infections accounted for 73% of the cases. Half of the patients in this survey received proton pump inhibitors within 90 days of diagnosis, and 79% received antimicrobial agents within 30 days of diagnosis. The most common antimicrobials associated with CDI in this survey were cephalosporins, fluoroquinolones, piperacillin-tazobactam, and carbapenems. The survey did not address types of acid-suppression therapy.

When analyzing CDI, it is imperative to have standardized surveillance methods. This includes classifying the infection according to when and how it was acquired.[1] Three categories are used to differentiate patients by the type of infection. The categories were first published in 2007 and are now recommended by the newest clinical practice guidelines of the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).[1,16] These categories have also been used in other studies, including the survey mentioned above,[7] and are as follows:

  • Community-associated C. difficile infection (CA-CDI): symptom onset before admission or within 48 hours of admission to a health care facility, and the last admission to a health care facility was more than 12 weeks before the new admission.

  • Community-onset, health care facility–associated disease (CO-HCFA): symptom onset before admission or within 48 hours of admission, but the last discharge from a health care facility was within the previous 4 weeks.

  • Health care facility–onset, health care facility– associated disease (HO-HCFA): symptom onset more than 48 hours from admission to a health care facility.

With the recent publication of the surveys above and the SHEA-IDSA clinical practice guidelines,[1] it is important to determine the rates of CDI at health care facilities and identify which drugs are risk factors. Results could then be compared with national estimates and used to determine areas of intervention for health care providers. These interventions could decrease the occurrences of CDI and improve patient outcomes.

Thus, the primary objectives of this study were to determine the incidence of Clostridium difficile infection (CDI) at one community hospital by identifying patients with stool samples positive for C. difficile toxin A or B, and to compare the incidence with a 2008 national estimate; and to determine which patient characteristics and concomitant antimicrobial and acid-suppression drugs are risk factors for the development of CDI. The secondary objective was to classify the origin of the CDI infection based on current guidelines—CA-CDI, CO-HCFA, or HO-HCFA.

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