Between 1991 and 2002 the frequency of times that either therapy was changed to vancomycin or vancomycin was added to metronidazole was unchanged (9.6%). During 2003-2004 this more than doubled (25.7%). The number of patients experiencing recurrence over a two-month period comparing data from 1991-2002 to 2003- 2004 was staggering (20.8% versus 47.2%; p<.001). The authors noted that as patients aged the probabilities of recurrence increased.
They also found that a subgroup of patients with a white blood cell count over 20,000 cells/mm3 and an elevated creatinine had a high short-term mortality rate.
Why might we be seeing these results? Several theories exist. Patients are both older and sicker than they have been in the past. Our antibiotic choice is changing with an increase in using agents that provide a more broad-spectrum coverage. Immune responses vary with fewer antitoxin antibodies found in those patients with symptoms and/or recurrence. Metronidazole levels in stool decrease as inflammation and diarrhea resolve; this is not the case with vancomycin where fecal concentrations remain high throughout treatment.
A survey of infectious disease physicians found that they believe antibiotic failure is on the rise in this setting. Before we take this as true, consider the following:
- We have no universally accepted clinical definition of what constitutes diarrhea for CDAD;
- Previous studies did not look for recurrence as far out from initial treatment as these two did; and
- These studies do not have the design to support arguments powerful enough to change our paradigm just yet.
The editorial comment acknowledged the Pepin, et al., report that patients with a high white blood cell count and worsening renal function are those that we should be particularly concerned about. The authors write that if the patient’s white blood cell count is increasing while on therapy that he changes his antibiotic choice to vancomycin. In addition, if someone has either ileus or fulminant CDAD he will use multiple antibiotics and consult the surgeons. At this time we have other agents being studied for CDAD, such as tinidazole. We now need a larger randomized prospective trial to better explore treatment outcomes in CDAD.
HYPERTONIC SALINE SOLUTION TO TREAT REFRACTORY CONGESTIVE HEART FAILURE
Paterna S, Di Pasquale P, Parrinello G, et al. Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose furosemide alone in refractory congestive heart failure. J Am Coll Cardiol. 2005;45:1997–2003.
CHF continues to increase in prevalence and incidence, despite our advances with therapies using ACE inhibitors, beta-blockers, and aldosterone antagonists. Refractory CHF accounts for a considerable portion of admissions to hospitalists’ services. Loop diuretics are part of the standard of arsenal we employ in these patients. Unfortunately, many patients fail to respond to initial diuretic doses. In this situation we might begin a constant infusion of diuretic or recruit diuretics from other classes in hope of synergism. Another typical approach in treating advanced CHF is restriction of sodium intake.
Paterna, et al., previously published four studies using small volume hypertonic saline solution and high-dose furosemide in refractory CHF, in which they demonstrated the safety and tolerability of these measures. They now present the first randomized double-blinded trial using this intervention. Ninety-four patients were included with NYHA functional class IV CHF on standard medical therapy and high doses of diuretics for at least two weeks. They had to have a left ventricular ejection fraction of <35%, serum creatinine <2 mg/dL, reduced urinary volume (<500 mL/24 h), and a low natriuresis (<60 mEq/24 h). They could not be taking NSAIDs.