Preferred First-Line Treatment for C difficile Diarrhea Has Worse Outcome, Higher Costs

Chris Berrie, MA, MPhil, PhD

April 05, 2007

April 5, 2007 (Munich, Germany) — A database comparison of demographics, risk factors, and hospital outcomes for patients with Clostridium difficile–associated diarrhea (CDAD) shows that the preferred first-line use of metronidazole (MET) is associated with worse discharge outcomes and higher total costs than the alternative use of vancomycin (VANC). The analysis was presented here at the joint 17th European Congress of Clinical Microbiology and Infectious Diseases and 25th International Congress on Chemotherapy.

According to treatment guidelines, the present treatment of choice for CDAD is MET for first-line therapy, while VANC is favoured for severe disease, treatment failure, and disease recurrence. However, the disease burden of CDAD is increasing worldwide, and recent reports have shown an increase in treatment failure and CDAD recurrence with the present standard treatments.

To assess these worrying trends, David M. Davidson, MD, senior medical director for drug and biomaterial research and development with the Genzyme Corporation in Waltham, Massachusetts, and colleague presented their database analysis that was designed to determine the extent of these effects on the treatment of CDAD in the United States.

The Premier Perspective Comparative Database was accessed based on the International Classification of Diseases, 9th Edition (ICD-9). Dr. Davidson pointed out, "The importance of this study is that the ICD-9 code for C difficile infection, 008.45, is sensitive and specific for making the diagnosis."

This database contains the largest collection of US hospital clinical and economic information, and it is compiled through monthly data reports from 460 hospitals, including more than 5 million hospital discharges and 20 million outpatient cases that are processed annually.

The investigators examined the database for ICD-9 code 008.45 between January 2004 and June 2005, selecting those patients whose pharmacy record indicated treatment with oral MET or oral VANC, with the addition of a "suspected oral VANC" group. This last was defined as a pharmacy record for intravenous VANC without evidence of accompanying intravenous administration (seen with almost 50% of VANC), as outpatient oral VANC use in the United States is often via the cheaper intravenous formulation.

Patients who were excluded had no CDAD therapy (8.9%), simultaneous MET and VANC therapy (1.9%), or intravenous MET as first therapy (4.0%).

The researchers found that there was a much greater use of first-line MET (n = 28,905) compared with VANC (n = 3420). Patients receiving first-line MET and VANC were a mean age of 70.2 years and 70.5 years, respectively, and 42.1% vs 37.3% were men ( P < .0001).

Comparison of the All Patient Refined-Diagnosis Related Grouping (APR-DRG) severity of illness ratings showed a significant trend ( P < .0001) for MET use for more severe disease. This was also reflected in the "extremely ill" grade 4 severity, represented by 30.5% of the MET group and 24.1% of the VANC group.

"However, as you would expect," Dr. Davidson said, "more vancomycin patients had a history of a prior CDAD admission." This reached significance, with 10.4% of those treated with MET and 30.7% of those treated with VANC ( P < .0001), and the VANC group was also slightly more likely to have had prior acid suppressive therapy (42.1% vs 53.1%, respectively; P < .0001).

The intensive care unit (ICU) length of stay was similar between MET and VANC groups (6.8% vs 6.6%), although MET use required a significant extra day in hospital (12.8 vs 11.5 days; P < .0001).

Regarding discharge outcomes, Dr. Davidson noted that they were not adjusted for comorbidities: "Here we see that metronidazole patients seemed to do less well than vancomycin patients" (MET vs VANC): death, 7.9% vs 6.8% ( P < .0001); ICU stay, 23.2% vs17.7% ( P < .0001); additional care on discharge, 31.0% vs29.4% ( P = .049).

Although MET cost less than VANC per discharge ($90 vs $375; P <.0001) and the total pharmacy costs were similar ($2439 vs $2492), the total hospital cost per discharge was significantly greater for patients in the MET group ($16,953 vs $14,718; P < .0001).

Thus, although this study highlighted a number of problems associated with the choice of first-line treatment of CDAD, as Dr. Davidson stressed, "Clearly further research is required to compare treatment outcomes of CDAD therapies and to control for patient-level factors."

Joint 17th European Congress of Clinical Microbiology and Infectious Diseases and 25th International Congress of Chemotherapy: Abstract O331. Presented April 2, 2007.

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