Bad Bugs: They don't call it C. "difficile" for nothing (Review, CHEST)
C. difficile has always been a foul and disgusting adversary, but lately it's becoming more formidable and deadly, according to Linda Bobo, Erik Dubberke and Marin Kollef. A few highlights of this excellent review:
C.diff infections (CDI) have more than doubled since 2001, to > 340,000 discharges in 2008.
Attributable mortality is 6-7%, but may be >15% during severe outbreaks.
There's a new, hypervirulent and lethal strain circulating; you needn't test for it or treat it any differently, but be aware.
>90% of people hospitalized for C.diff previously received a fluoroquinolone, clindamycin, or cephalosporin.
Most are not febrile (30%).
Supposedly only 50% have an elevated white blood cell count, but WBC >20K can be a sign of fulminant colitis progressing to shock.
As many as 20% of hospitalized patients, and 50% of long-term care residents, may be asymptomatic carriers of C. diff.
Interestingly, the true sensitivity and specificity of C.difficile toxin assays are simply not known. Authors don't believe the quoted statistics because they believe they're contaminated by asymptomatic carriers being included in those studies.
Authors recommend not testing people with formed stools (who by definition do not have C. difficile infection), and not automatically repeating a test after a negative result (unlike what I was taught in residency, which was to test 3 times). In short, they advise placing the results in clinical context (presentation, imaging, and endoscopy).
Recurrence rate is a stubborn 30%, and once there has been one recurrence, another is 60% likely. Initial treatment (vanco vs. Flagyl) does not change recurrence risk.
Mild/moderate disease: Metronidazole 500 mg po tid;
Severe or multiply recurrent disease: Vancomycin 125 mg po qid;
Hemodynamically unstable patients: Metronidazole IV and higher dose of oral vancomycin, plus a surgical consult as colectomy may be needed.
Consider IVIG 200-500 mg/kg for fulminant colitis or as salvage therapy (conflicting data).
Multiple recurrence: taper oral vancomycin over months.
Bacteriotherapy (stool transplantation from healthy donors) has had anecdotal success rates of 80% (but has not been reported in ICU patients with severe infection)
Other agents are unproven or experimental: cholestyramine (binds vancomycin), tigecycline, nitazoxanide, probiotics.
Fidaxomycin passed phase 3 trials and will likely be available soon.
There's no way to predict whose symptoms will progress to severe disease. Even people who end up with life-threatening C. diff often start with mild symptoms, so there's no way to decide to whom to give empiric oral vancomycin at the outset.
Colectomy is necessary and may be lifesaving in those with fulminant colitis, but mortality is 35-60% regardless. Watch for severe abdominal pain and stoppage of diarrhea as heralds of toxic megacolon/fulminant colitis.
Bobo L et al. Clostridium difficile in the ICU. The Struggle Continues. CHEST 2011;140:1643-1653.