AUTHOR Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

PEER REVIEWER Gerald Roberts, MD Senior Attending Physician Long Island Jewish Medical Center NS/LIJ Health Care System New Hyde Park, NY

SOURCE: Brown AT, et al. Effect of treatment variation on outcomes in patients with Clostridium difficile. Am J Med 2014;127:865-870.

Formal recommendations for the treatment of C. difficile infection (CDI), based on expert opinion and available literature, were published by the Infectious Disease Society of America (IDSA) in 2010.1 These authors performed a retrospective study for 6 months in 2011, evaluating the effectiveness of the IDSA guideline-directed CDI treatment compared with alternate treatment at their tertiary care county teaching hospital. IDSA recommendations for CDI treatment are included in Table 1. Patients with CDI were identified based on ICD-9 coding at discharge and treatment for CDI infection. Demographic information was collected, and patients were classified as mild-to-moderate, severe, or severe-complicated based on the IDSA guidelines. The primary outcome of study was the occurrence of complications, including relapse within 4 weeks, surgery, toxic megacolon, and 30-day mortality. Secondary outcomes included length of stay and clinical cure.

 

Clinical Definition

Supportive Clinical Data

Recommended Treatment

Strength of
Recommendation

Reprinted with permission from: Cohen SH, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-455.

Initial episode, mild or moderate

Leukocytosis with a white blood cell count of 15,000 cells/μL or lower and a serum creatinine level < 1.5 times the premorbid level

Metronidazole, 500 mg 3 times per day by mouth for 10-14 days

A-I

Initial episode, severe

Leukocytosis with a white blood cell count of 15,000 cells/μL or higher or a serum creatinine level ≥ 1.5 times the premorbid level

Vancomycin, 125 mg 4 times per day by mouth for 10-14 days

B-I

Initial episode, severe, complicated

Hypotension or shock, ileus,
megacolon

Vancomycin, 500 mg 4 times per day by mouth or by nasogastric tube, plus metronidazole, 500 mg every 8 hours intravenously. If complete ileus, consider adding rectal instillation of vancomycin.

C-III

First recurrence

Same as for initial episode

A-II

Second recurrence

Vancomycin in a tapered or pulsed regimen

B-III

A total of 180 adults with CDI met criteria for inclusion in the study, 93 of whom (52%) were treated in accordance with the IDSA guidelines. The two groups (guideline-directed care and alternate care) were similar with respect to race and classification of disease severity, although those who received alternate care tended to be older and were more likely male. Only 116 (64%) of the participants had received antibiotics within the previous 8 weeks. In these subjects, antibacterials were used for an average of 8 days ± 10 days. Quinolones were received more often (32%) than other agents. In addition, proton pump therapy was administered within the previous 8 weeks to 100 patients (55%).

The NAP-1 strain was identified in 37% of the group receiving guideline-directed care, compared with 41.4% of the group receiving alternate care (P = NS), although was more frequently identified in patients with severe/complicated infection. Patients with the NAP-1 strain had a higher rate of ICU admission and significantly higher risk of mortality.

Guideline-directed care was associated with significantly fewer complications than alternate care (17.2% vs 56.3%; P < .0001). This was due in large part to a lower rate of mortality in persons receiving guideline-directed care compared with those in the alternate therapy group (5% vs 21.8%, P = 0.0012), as well as a lower rate of recurrence (14% vs 35.6%, P = 0.0007). Clinical cures were more frequent in patients receiving guideline-directed care compared with alternate care (93.5% vs 71.3%). Multiple logistical regression analysis demonstrated that relapses were 72% less likely in patients receiving guideline-directed care compared with alternate care.

Guideline-directed care was more often used in patients with mild-to-moderate disease (81%) compared with those with severe disease (35%) or those with severe-complicated disease (19.7%). The main reasons for patients with severe disease not meeting criteria for guideline-directed care included the use of flagyl as a single agent (55%) and failure to receive a taper or pulse therapy in those with multiple recurrences (23%). The main reasons for patients with severe-complicated disease not meeting criteria for guideline-directed care were the use of flagyl as single agent (57%) and the use of oral vancomycin without parenterally administered flagyl (35%).

In conclusion, many of the patients with CDI in this study were initially treated with flagyl regardless of their disease classification which meant those with mild-to-moderate disease met the guidelines (and did well), while many of those with more severe disease received inadequate therapy with flagyl or vancomycin alone, with a resulting increased risk of complications and mortality.

COMMENTARY

Treatment based on the IDSA guidelines appears to improve outcomes, with a lower risk of relapse, surgery, and death, and should be broadly implemented. Teaching hospitals, in particular, have a responsibility to train and educate their house staff about the use of currently recommended therapies.

REFERENCES

1. Cohen SH, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;3:431-455.