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Lactobacillus Species Can Cause a False-positive Test for Hematuria on Dipstick Urinalysis
CLINICAL COMMUNICATION TO THE EDITOR
Lactobacillus Species Can Cause a Falsepositive Test for Hematuria on Dipstick Urinalysis To the Editor: The dipstick urinalysis offers a convenient method for analyzing the composition of urine. Detection of hematuria on the urine dipstick relies on the pseudoperoxidase activity of hemoglobin to catalyze the oxidation of a benzidine compound by reduction of a buffered organic peroxide.1 False-positive tests for hematuria can be caused by agents that either catalyze this reaction or directly oxidize the substrate, including myoglobin, semen, sodium hypochlorite, povidone-iodine, and bacterial or vegetable peroxidases.2 A false-positive test should be considered when a dipstick finding is not confirmed by direct visualization of erythrocytes in the urine. False-positive tests may result in unnecessary patient anxiety, excessive costs, and potential morbidity from unnecessary follow-up testing.3 Two patients, a 64-year-old African American woman (Case 1) and a 41-year-old European American woman (Case 2), presented for evaluation of hematuria detected on dipstick urinalysis. Evaluation had included imaging of the urinary tract and cystoscopy, all unremarkable. The latter patient had undergone kidney biopsy, which showed normal histology. Upon referral, neither patient had evidence of intravascular hemolysis or myoglobinuria. Urine dipstick tests showed hematuria, no leukocyte esterase, and no nitrites. Examination of the urine sediment demonstrated rodshaped bacteria and no erythrocytes. Urine cultures grew Lactobacillus species ⬎100,000 cfu/mL. The cultured lactobacilli and a selection of other bacterial isolates were suspended in saline and tested with urine dipsticks. Lactobacillus species caused a positive test for blood (large, 3⫹), as did other bacteria to varying degrees
Funding: None. Conflict of Interest: None. Authorship: All authors had full access to the data for this study and had a role in writing this manuscript. Requests for reprints should be addressed to James L. Pirkle Jr, MD, Section on Nephrology, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1053. E-mail address: [email protected]
0002-9343/$ -see front matter © 2013 Elsevier Inc. All rights reserved.
Table
Urine Dipstick Testing of Bacterial Isolates in Saline Urine Dipstick Test for Blood†
Organism* Clinical case isolates Case 1 Lactobacillus species Case 2 Lactobacillus species Clinical laboratory isolates (from additional cases) Lactobacillus species Enterococcus faecium Coagulase-negative Staphylococcus Escherichia coli Laboratory reference strains Staphylococcus aureus ATCC 29213 Pseudomonas aeruginosa ATCC 27853 Escherichia coli ATCC 25922 Proteus vulgaris ATCC 49132 Enterococcus faecalis ATCC 29212 Klebsiella pneumoniae ATCC 700603 Saline control
Large (3⫹) Large (3⫹)
Large (3⫹) Small (1⫹) Trace Trace Large (3⫹) Moderate (2⫹) Moderate (2⫹) Trace Trace Trace Negative
*⬃105 cfu/mL suspended in 5 cc 0.85% saline. †All results had homogeneous color change, suggesting the presence of hemolyzed blood.
(Table). In 2 successive examinations, urinalysis and culture findings in both patients yielded similar results. Bacterial peroxidases are known to cause false-positive tests for hematuria; however, this possibility may not be considered when nonpathogenic bacteria are present. A simple dipstick urinalysis may not identify nonpathogenic bacteria in the urine because of the lack of signs of infection, such as leukocyte esterase and nitrites. For similar reasons, a urine culture is not likely to be performed in such cases. Lactobacilli are part of the normal bacterial flora of the distal urethra and vagina, and many strains produce hydrogen peroxide, which aids in host defenses.4 It is not uncommon to culture lactobacilli from the urine of women in the absence of clinical infection.5 Lactobacilli may cause false-positive tests for hematuria via production of hydrogen peroxide, which can directly oxidize the benzidine compound, or by a bacterial peroxidase-mediated mechanism. James L. Pirkle, MDa Elizabeth L. Palavecino, MDb Barry I. Freedman, MDa a
Department of Internal Medicine Section on Nephrology b Department of Pathology
e4
The American Journal of Medicine, Vol 126, No 1, January 2013 Wake Forest School of Medicine Winston-Salem, NC
http://dx.doi.org/10.1016/j.amjmed.2012.07.017
References 1. U.S. Patent 4755472. Stable composition for the determination of peroxidatively active substances. Issued July 5, 1988.
2. Wilson DM. Urinalysis and other tests of renal function. Minn Med. 1975;58(1):9-17. 3. Rao PK, Gao T, Pohl M, Jones JS. Dipstick pseudohematuria: unnecessary consultation and evaluation. J Urol. 2010;183(2):560564. 4. Aroutcheva A, Gariti D, Simon M, et al. Defense factors of vaginal lactobacilli. Am J Obstet Gynecol. 2001;185:375-379. 5. Maskell R, Pead L, Sanderson RA. Fastidious bacteria and the urethral syndrome: a 2-year clinical and bacteriological study of 51 women. Lancet. 1983;2(8362):1277-1280.
Lactobacillus Species Can Cause a Falsepositive Test for Hematuria on Dipstick Urinalysis To the Editor: The dipstick urinalysis offers a convenient method for analyzing the composition of urine. Detection of hematuria on the urine dipstick relies on the pseudoperoxidase activity of hemoglobin to catalyze the oxidation of a benzidine compound by reduction of a buffered organic peroxide.1 False-positive tests for hematuria can be caused by agents that either catalyze this reaction or directly oxidize the substrate, including myoglobin, semen, sodium hypochlorite, povidone-iodine, and bacterial or vegetable peroxidases.2 A false-positive test should be considered when a dipstick finding is not confirmed by direct visualization of erythrocytes in the urine. False-positive tests may result in unnecessary patient anxiety, excessive costs, and potential morbidity from unnecessary follow-up testing.3 Two patients, a 64-year-old African American woman (Case 1) and a 41-year-old European American woman (Case 2), presented for evaluation of hematuria detected on dipstick urinalysis. Evaluation had included imaging of the urinary tract and cystoscopy, all unremarkable. The latter patient had undergone kidney biopsy, which showed normal histology. Upon referral, neither patient had evidence of intravascular hemolysis or myoglobinuria. Urine dipstick tests showed hematuria, no leukocyte esterase, and no nitrites. Examination of the urine sediment demonstrated rodshaped bacteria and no erythrocytes. Urine cultures grew Lactobacillus species ⬎100,000 cfu/mL. The cultured lactobacilli and a selection of other bacterial isolates were suspended in saline and tested with urine dipsticks. Lactobacillus species caused a positive test for blood (large, 3⫹), as did other bacteria to varying degrees
Funding: None. Conflict of Interest: None. Authorship: All authors had full access to the data for this study and had a role in writing this manuscript. Requests for reprints should be addressed to James L. Pirkle Jr, MD, Section on Nephrology, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1053. E-mail address: [email protected]
0002-9343/$ -see front matter © 2013 Elsevier Inc. All rights reserved.
Table
Urine Dipstick Testing of Bacterial Isolates in Saline Urine Dipstick Test for Blood†
Organism* Clinical case isolates Case 1 Lactobacillus species Case 2 Lactobacillus species Clinical laboratory isolates (from additional cases) Lactobacillus species Enterococcus faecium Coagulase-negative Staphylococcus Escherichia coli Laboratory reference strains Staphylococcus aureus ATCC 29213 Pseudomonas aeruginosa ATCC 27853 Escherichia coli ATCC 25922 Proteus vulgaris ATCC 49132 Enterococcus faecalis ATCC 29212 Klebsiella pneumoniae ATCC 700603 Saline control
Large (3⫹) Large (3⫹)
Large (3⫹) Small (1⫹) Trace Trace Large (3⫹) Moderate (2⫹) Moderate (2⫹) Trace Trace Trace Negative
*⬃105 cfu/mL suspended in 5 cc 0.85% saline. †All results had homogeneous color change, suggesting the presence of hemolyzed blood.
(Table). In 2 successive examinations, urinalysis and culture findings in both patients yielded similar results. Bacterial peroxidases are known to cause false-positive tests for hematuria; however, this possibility may not be considered when nonpathogenic bacteria are present. A simple dipstick urinalysis may not identify nonpathogenic bacteria in the urine because of the lack of signs of infection, such as leukocyte esterase and nitrites. For similar reasons, a urine culture is not likely to be performed in such cases. Lactobacilli are part of the normal bacterial flora of the distal urethra and vagina, and many strains produce hydrogen peroxide, which aids in host defenses.4 It is not uncommon to culture lactobacilli from the urine of women in the absence of clinical infection.5 Lactobacilli may cause false-positive tests for hematuria via production of hydrogen peroxide, which can directly oxidize the benzidine compound, or by a bacterial peroxidase-mediated mechanism. James L. Pirkle, MDa Elizabeth L. Palavecino, MDb Barry I. Freedman, MDa a
Department of Internal Medicine Section on Nephrology b Department of Pathology
e4
The American Journal of Medicine, Vol 126, No 1, January 2013 Wake Forest School of Medicine Winston-Salem, NC
http://dx.doi.org/10.1016/j.amjmed.2012.07.017
References 1. U.S. Patent 4755472. Stable composition for the determination of peroxidatively active substances. Issued July 5, 1988.
2. Wilson DM. Urinalysis and other tests of renal function. Minn Med. 1975;58(1):9-17. 3. Rao PK, Gao T, Pohl M, Jones JS. Dipstick pseudohematuria: unnecessary consultation and evaluation. J Urol. 2010;183(2):560564. 4. Aroutcheva A, Gariti D, Simon M, et al. Defense factors of vaginal lactobacilli. Am J Obstet Gynecol. 2001;185:375-379. 5. Maskell R, Pead L, Sanderson RA. Fastidious bacteria and the urethral syndrome: a 2-year clinical and bacteriological study of 51 women. Lancet. 1983;2(8362):1277-1280.