T h e ne w e ngl a nd jou r na l o f m e dic i ne
`
`previously treated with fluconazole. A random-
`ized trial comparing the efficacy of voriconazole
`with that of echinocandins for the treatment of
`candidemia is warranted.
`Carolina Garcia-Vidal, M.D.
`Jordi Carratalà, M.D.
`Hospital Universitari de Bellvitge
`08907 Barcelona, Spain
`Dr. Carratalà reports receiving lecture fees from Pfizer.
`
`Bennett JE. Echinocandins for candidemia in adults without
`1.
`neutropenia. N Engl J Med 2006;355:1154-9.
`Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a
`2.
`regimen of amphotericin B followed by fluconazole for candidae-
`mia in non-neutropenic patients: a randomised non-inferiority
`trial. Lancet 2005;366:1435-42.
`Ostrosky-Zeichner L, Rex JH, Pappas PG, et al. Antifungal
`3.
`susceptibility survey of 2000 bloodstream Candida isolates in the
`United States. Antimicrob Agents Chemother 2003;47:3149-54.
`Panackal AA, Gribskov JL, Staab JF, et al. Clinical signifi-
`4.
`cance of azole antifungal drug cross-resistance in Candida gla-
`brata. J Clin Microbiol 2006;44:1740-3.
`
`The author replies: The recently published
`Swiss guidelines concur with the view of Garcia-
`Vidal and Carratalà that voriconazole should be
`considered as one of the second-line agents for
`treatment of candidemia in nonneutropenic pa-
`
`tients with no prior exposure to an azole.1 How-
`ever, I see no clear indication for selecting vori-
`conazole over fluconazole for such patients.
`Candida species with reduced susceptibility to flu-
`conazole have proportionally reduced susceptibil-
`ity to voriconazole. The major indication for the
`use of voriconazole is its clinical efficacy against
`invasive mold infections.2 For candidemia, flucon-
`azole is the preferred azole because of its supe-
`rior safety profile, fewer known drug interactions,
`and lower cost, and because of the absence of
`restrictions on intravenous administration in pa-
`tients with a creatinine clearance below 50 ml per
`minute.3
`John E. Bennett, M.D.
`National Institute of Allergy and Infectious Diseases
`Bethesda, MD 20892
`
`Flückiger U, Marchetti O, Bille J, et al. Treatment options of
`1.
`invasive fungal infections in adults. Swiss Med Wkly 2006;136:
`447-63.
`Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole
`2.
`versus amphotericin B for primary therapy of invasive aspergillo-
`sis. N Engl J Med 2002;347:408-15.
`Kofla G, Ruhnke M. Voriconazole: review of a broad spectrum
`3.
`triazole antifungal agent. Expert Opin Pharmacother 2005;6:
`1215-29.
`
`Effects of Dietary Nitrate on Blood Pressure in Healthy Volunteers
`To the Editor: Nitric oxide, generated by nitric
`days. The compounds were dissolved in water and
`oxide synthase, is a key regulator of vascular integ-
`could not be distinguished by taste or appearance.
`rity. This system is dysfunctional in many cardio-
`During the two treatment periods, the subjects
`vascular disorders, including hypertension. A fun-
`were instructed to avoid all foods with a moder-
`ate or high nitrate content.3
`damentally different pathway for the generation
`of nitric oxide was recently described in which the
`Systolic blood pressure (Fig. 1A) and pulse rate
`–) are con-
`–) and nitrite (NO2
`anions nitrate (NO3
`did not change significantly after nitrate supple-
`verted into nitric oxide and other bioactive nitro-
`mentation, as compared with placebo supplemen-
`gen oxides.1-3 Nitrate is abundant in our diet, and
`tation. However, the diastolic blood pressure was
`particularly high levels are found in many vege-
`on average 3.7 mm Hg lower after nitrate supple-
`tables.3
`mentation than after placebo supplementation
`We examined the effect of 3-day dietary sup-
`(P<0.02) (Fig. 1B), and the mean arterial pressure
`plementation with either sodium nitrate (at a dose
`was 3.2 mm Hg lower (P<0.03). Plasma nitrate
`of 0.1 mmol per kilogram of body weight per
`levels were higher after nitrate ingestion than
`day) or placebo (sodium chloride, at a dose of
`after placebo ingestion (mean [±SD], 178±51 and
`0.1 mmol per kilogram per day) on blood pressure
`26±11 μM, respectively; P<0.001), as were plasma
`in 17 physically active, healthy volunteers, none of
`nitrite levels (219±105 and 138±38 nM, respec-
`whom smoked (15 men and 2 women; mean age,
`tively; P<0.01).
`24 years). The study had a randomized, double-
`The daily nitrate dose used in the study corre-
`blind, crossover design with two different treat-
`sponds to the amount normally found in 150 to
`ment periods during which the subjects received
`250 g of a nitrate-rich vegetable such as spinach,
`either nitrate or placebo; the treatment periods
`beetroot, or lettuce. It is clear from earlier studies,
`were separated by a washout period of at least 10
`such as the Dietary Approaches to Stop Hyperten-
`
`2792
`
`n engl j med 355;26 www.nejm.org december 28, 2006
`
`The New England Journal of Medicine
`
`Downloaded from nejm.org by Michael Pohl on March 19, 2021. For personal use only. No other uses without permission.
`
` Copyright © 2006 Massachusetts Medical Society. All rights reserved.
`
`Human Power of N Company
`EX1040
`Page 1 of 2
`
`

`

`correspondence
`
`sure was associated with nitrate supplementation
`alone; this effect was evident in young normoten-
`sive subjects. In fact, it was similar to that seen
`in the healthy control group in the DASH study.4
`The exact mechanism behind the blood-pressure–
`lowering effect of nitrate needs to be clarified in
`future studies.
`We conclude that short-term dietary supple-
`mentation with inorganic nitrate reduces diastolic
`blood pressure in healthy young volunteers.
`Filip J. Larsen, M.Sc.
`Björn Ekblom, M.D., Ph.D.
`Kent Sahlin, Ph.D.
`Swedish School of Sport and Health Sciences
`S-11433 Stockholm, Sweden
`Jon O. Lundberg, M.D., Ph.D.
`Eddie Weitzberg, M.D., Ph.D.
`Karolinska Institutet
`S-17177 Stockholm, Sweden
`eddie.weitzberg@ki.se
`Supported by grants from the Swedish Research Council, the
`Swedish Heart and Lung Foundation, and the European Commu-
`nity’s Sixth Framework Program (Eicosanox, LSMH-CT-2004-
`005033).
`Lundberg JO, Weitzberg E. NO generation from nitrite and
`1.
`its role in vascular control. Arterioscler Thromb Vasc Biol 2005;
`25:915-22.
`Gladwin MT, Schechter AN, Kim-Shapiro DB, et al. The emerg-
`2.
`ing biology of the nitrite anion. Nat Chem Biol 2005;1:308-14.
`[Erratum, Nat Chem Biol 2006;2:110.]
`Lundberg JO, Weitzberg E, Cole JA, Benjamin N. Nitrate,
`3.
`bacteria and human health. Nat Rev Microbiol 2004;2:593-602.
`[Erratum, Nat Rev Microbiol 2004;2:681.]
`Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the
`4.
`effects of dietary patterns on blood pressure. N Engl J Med 1997;
`336:1117-24.
`Rouse IL, Beilin LJ, Armstrong BK, Vandongen R. Blood-
`5.
`pressure-lowering effect of a vegetarian diet: controlled trial in
`normotensive subjects. Lancet 1983;1:5-10.
`Correspondence Copyright © 2006 Massachusetts Medical Society.
`
`Placebo
`
`Nitrate
`
`Placebo
`
`Nitrate
`
`130
`
`120
`
`110
`
`100
`
`90
`
`0
`
`90
`
`80
`
`70
`
`60
`
`50
`
`0
`
`A
`
`(mm Hg)
`
`Systolic Blood Pressure
`
`B
`
`(mm Hg)
`
`Diastolic Blood Pressure
`
`Figure 1. Effects of 3-Day Dietary Supplementation
`with Inorganic Nitrate or Placebo on Systolic (Panel A)
`and Diastolic (Panel B) Blood Pressure in 17 Healthy
`Volunteers.
`The diastolic pressure was reduced by 3.7 mm Hg after
`nitrate supplementation (P<0.02), whereas systolic blood
`pressure was not significantly changed.
`
`sion (DASH) trial, that a diet rich in fruits and
`vegetables can reduce blood pressure,4,5 but at-
`tempts to modify single nutrients have been in-
`consistent. Therefore, it has been argued that the
`effect of any individual nutrient is too small to
`detect in trials. In our study, reduced blood pres-
`
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`n engl j med 355;26 www.nejm.org december 28, 2006
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`2793
`
`The New England Journal of Medicine
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