Document Detail

In vitro evaluation of a new treatment for urinary tract infections caused by nitrate-reducing bacteria.
MedLine Citation:
PMID:  14638471     Owner:  NLM     Status:  MEDLINE    
Dietary and endogenous nitrates are excreted in urine, and during infection with nitrate-reducing bacteria they are reduced to nitrite. At a low pH nitrite is converted to a variety of nitrogen oxides that are toxic to bacteria. We hypothesized that acidification of nitrite-rich infected urine would result in the killing of the nitrate-reducing bacteria. An Escherichia coli control strain and a mutant lacking nitrate reductase activity were preincubated in urine supplemented with sodium nitrate (0 to 10 mM) at pH 7.0. Then, the nitrite-containing bacterial culture was transferred (and diluted 1/10) to slightly acidic urine (pH 5 and 5.5) containing ascorbic acid (10 mM) and growth was monitored. The control strain produced nitrite in amounts related to the amount of nitrate added. This strain was killed when the culture was transferred to acidic urine. In contrast, the mutant that did not produce nitrite retained full viability. When control bacteria were grown in acidic urine with nitrate and ascorbic acid present from the start of the experiment, no inhibition of growth was noted. The MICs and minimal bactericidal concentrations of sodium nitrite-ascorbic acid in acidic urine were comparable to those of conventional antibiotics. Preincubation of nitrate-reducing E. coli in nitrate-rich urine leads to the accumulation of nitrite. Subsequent acidification of the urine results in generation of nitrogen oxides that are bactericidal. Killing, however, requires a sequential procedure in which the bacteria are first allowed to grow in a nitrate-rich neutral environment, later followed by acidification. We speculate that ingestion of nitrate followed some hours later by acidification of urine could be a new therapeutic strategy for the treatment of urinary tract infections.
S Carlsson; M Govoni; N P Wiklund; E Weitzberg; J O Lundberg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  47     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-25     Completed Date:  2004-01-13     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3713-8     Citation Subset:  IM    
Department of Surgery, Section of Urology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
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MeSH Terms
Anti-Infective Agents, Urinary / pharmacology,  therapeutic use
Colony Count, Microbial
Escherichia coli / drug effects,  genetics,  metabolism*
Hydrogen-Ion Concentration
Microbial Sensitivity Tests
Middle Aged
Nitrates / metabolism*,  urine
Nitrites / metabolism,  urine
Nitrofurantoin / pharmacology,  therapeutic use
Sodium Nitrite / metabolism,  pharmacology
Trimethoprim / pharmacology,  therapeutic use
Urinary Tract Infections / drug therapy*,  microbiology*
Reg. No./Substance:
0/Anti-Infective Agents, Urinary; 0/Nitrates; 0/Nitrites; 67-20-9/Nitrofurantoin; 738-70-5/Trimethoprim; 7632-00-0/Sodium Nitrite

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