By Carol A. Kemper, MD, FACP

Fecal Carriage of VRE

Source: Donskey CJ, et al. Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients. N Engl J Med. 2000;343:1925-1932.

Donskey and associates exam-ined the effect of various antibiotic regimens on the fecal carriage of vancomycin-resistant enterococcus (VRE) in 55 patients with pre-existing colonization. The density of VRE in stools was significantly increased within 1 week of administration of agents with antianaerobic activity, including such agents as amoxacillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam, imipenem-cilastin, cefoxitin, ceftriaxone, clindamycin, metronidazole, and vancomycin. High levels of fecal colonization with VRE were maintained in these patients as long as the antibiotics were continued (mean, 7.8 logs of VRE/g of stool), irrespective of the mode of administration (oral vs parenteral).

Once the antibiotics were discontinued, the density of VRE in stool began to fall in all subjects within 4 weeks. But it took an average of 17.4 weeks (range, 6-20) after the discontinuation of antibiotics before VRE were no longer detectable in stools. In addition, colonization with VRE decreased among 10 patients who received agents with minimal antianaerobic activity, including dicloxacillin, cephalexin, levofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole.

Environmental samples collected from the rooms of patients with fecal incontinence were significantly more likely to be positive for VRE if the patient had high levels of VRE in stool. Sets of environmental samples had at least 1 positive specimen in 83% of patients with high levels of fecal carriage (³ 4.0 logs/g) vs. only 11% of those with lower levels.

The good news from this report is that fecal carriage of VRE does eventually go away. The bad news is that these patients may present a transmission risk for up to 5 months—and that’s if they don’t receive any more "bad" antibiotics with anaerobic activity. For this reason, patients admitted to the hospital with a history of fecal colonization with VRE should be isolated with contact precautions, at least until they are cleared. Clinicians should presume that the immediate surroundings of these patients, especially those who are incontinent, are contaminated. The use of antibiotics with anaerobic activity (not just vancomycin!) should be limited and of the shortest duration as possible in patients with known fecal carriage of VRE.

Nonmeningeal Cocci: Is One Azole Better?

Source: Galgiani JN, et al. Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis. A randomized, double-blind trial. Mycoses Study Group. Ann Intern Med. 2000;133:676-686.

Galgiani and associates con-ducted a large-scale, randomized, double-blind, placebo-controlled trial of fluconazole vs. itraconazole in the treatment of nonmeningeal coccidioidomycosis. A total of 191 patients with chronic pulmonary (n = 70), soft tissue (n = 71), or skeletal (n = 50) cocci were randomized to receive either fluconazole 400 mg daily or itraconazole 200 mg twice daily for 12 months. Patients who had received more than 4 mg/kg of amphotericin B or more than 8 grams of an azole were excluded from study. HIV-infected patients were eligible if their CD4 count at the time of enrollment was greater than 250/mm3 (7 patients with HIV/AIDS were enrolled). Eighteen patients with both skeletal and soft tissue infection (5 of whom also had pulmonary involvement) were assigned to the skeletal group.

Both agents were similarly effective at 8 and 12 months of therapy, although there was a trend toward slightly greater efficacy with itraconazole. At 12 months, 57% of patients responded to fluconazole, whereas 72% responded to itraconazole (P = .05). This was largely the result of the poorer response of patients with skeletal infection to fluconazole compared with itraconazole (37% vs 69%; P = .03). In contrast, there was no apparent difference in the response between the two treatment groups for patients with soft tissue or pulmonary infection. In multivariate analysis, patients with soft tissue infection, a lack of dermal erythema overlying skeletal lesions, and no prior therapy for cocci infection were associated with higher rates of response.

A longer duration of therapy was associated with a greater likelihood of response, although a few patients responded to only 4 months of therapy. Serum azole concentrations, which were assessed after the close of study, were not associated with response.

Both drugs were well tolerated. One possible difference between the 2 therapies was unanticipated: alopecia and dry lips were reported in 15% and 11% of patients receiving fluconazole, compared with only 4% and 0% of patients receiving itraconazole. Earlier reports have suggested that cheilitis and xerosis may be related to the administration of fluconazole. These data suggest that about 63-79% of patients with nonmeningeal cocci may respond to either itraconazole or fluconazole, although itraconazole may be a better choice for the treatment of skeletal disease due to coccidioidomycosis.