A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity.

BACKGROUND: The incidence and severity of Clostridium difficile-associated diarrhea (CDAD) has been increasing, and there have been recent reports of metronidazole treatment failure. Metronidazole is still commonly used as first-line treatment for CDAD but has never been compared with vancomycin in a prospective, randomized, double-blind, placebo-controlled trial. We conducted such a trial, stratifying patients according to disease severity, to investigate whether one agent was superior for treating either mild or severe disease. METHODS: From October 1994 through June 2002, patients with CDAD were stratified according to whether they had mild or severe disease based on clinical criteria and were randomly assigned to receive oral metronidazole (250 mg 4 times per day) or oral vancomycin (125 mg 4 times per day) for 10 days. Both groups received an oral placebo in addition to the study drug. Patients were followed up for 21 days to assess cure, treatment failure, relapse, or intolerance. RESULTS: One hundred seventy-two patients were enrolled, and 150 of these patients successfully completed the trial. Among the patients with mild CDAD, treatment with metronidazole or vancomycin resulted in clinical cure in 90% and 98% of the patients, respectively (P=.36). Among the patients with severe CDAD, treatment with metronidazole or vancomycin resulted in clinical cure in 76% and 97% of the patients, respectively (P=.02). Clinical symptoms recurred in 15% of the patients treated with metronidazole and 14% of those treated with vancomycin. CONCLUSIONS: Our findings suggest that metronidazole and vancomycin are equally effective for the treatment of mild CDAD, but vancomycin is superior for treating patients with severe CDAD.

Distal renal tubular acidosis and the potassium enigma.

Severe hypokalemia is a central feature of the classic type of distal renal tubular acidosis (RTA), both in hereditary and acquired forms. In the past decade, many of the genetic defects associated with the hereditary types of distal RTA have been identified and have been the subject of a number of reviews. These genetic advances have expanded our understanding of the molecular mechanisms that lead to distal RTA. In this article, we review data published in the literature on plasma potassium from patients with inherited forms of distal RTA. The degree of hypokalemia varies depending on whether the disease is autosomal autosomal-recessive or dominant, but, interestingly, it occurs in defects caused by mutations in genes encoding the AE-1 exchanger, the carbonic anhydrase II gene, and genes encoding different subunits of the H+ adenosine triphosphatase. This shows that a unique defect involving the H+/K+-adenosine triphosphatase leading to renal potassium wastage cannot explain the hypokalemia seen in virtually all types of classic distal RTA.

Nocturnal hypertension: will control of nighttime blood pressure prevent progression of diabetic renal disease?

Patients with type 1 and 2 diabetes and nephropathy frequently have a blunted fall in nighttime arterial blood pressure. This abnormality is already seen in subjects with type 1 diabetes who are in the microalbuminuric phase of the disease, and we have also shown that an increase in nighttime systolic blood pressure precedes the development of microalbuminuria. These studies suggest that nocturnal hypertension may be an important early predictor of diabetic nephropathy. Various drugs have different effects on nocturnal blood pressure, and chronotherapy may be key in determining clinical outcomes. There is a compelling need for studies showing that treating nocturnal hypertension in diabetes can prevent renal disease progression.

Concentration of cefixime in bile, gallbladder wall and serum after preoperative administration in patients undergoing cholecystectomy.

Cefixime is a new oral cephalosporin antibiotic with improved activity against Gram-negative pathogens comparable to the parenteral third generation cephalosporins, high beta-lactamase stability and a long elimination half-life of about 3 h. 15 patients undergoing cholecystectomy received 2 x 200 mg/day cefixime for two days before surgery. The last application was administered 13-17 h preoperatively. Intraoperatively, the mean biliary level of cefexime was 199.3 micrograms/ml (8.8 micrograms/ml-1163.8 micrograms/ml). The mean level in gallbladder wall was 25.02 micrograms/g (0.68 micrograms/g-61.20 micrograms/g). Serum samples were taken simultaneously. Despite relevant concentrations in bile and gallbladder wall, no cefixime could be detected in the serum samples of two patients. The other 13 patients, however, showed relevant serum levels between 0.28 micrograms/ml and 2.98 micrograms/ml (mean 1.01 micrograms/ml). Side effects as well as an influence on laboratory parameters were not seen. After administration of cefixime in bile and gallbladder tissue high antibiotic levels were achieved, even 13-17 hours after the last application.

Is the administration of doxycycline still indicated in bacterial infections of the gallbladder and the bile ducts?

The levels of doxycycline in serum, bile and the gallbladder wall were determined in 25 patients during cholecystectomy, by means of bioassay after previous intravenous administration of doxycycline. The mean biliary level exceeded 20 microgram/ml, and the mean level in the gallbladder wall was greater than 2 microgram/g. With few exceptions all the levels found clearly exceeded the MIC of most relevant pathogens. This was confirmed by the levels found in bile drained via T-Tube. Thus, clinically important breakdown of doxycycline by the mainly alkaline bile acids should not be anticipated.