2 4 6 Brief clinical and laboratory observations
treated for seizure disorders is higher than in a nontreated group. Evidence has accumulated that a syndrome of facial cleft and other malformations, particularly minor ones of the extremities, occur in offspring of women with seizure disorders treated with anticonvulsants. Spidel and Meadow7 described the syndrome, and others have emphasized the minor skeletal abnormalities. One of our children may be included in this catagory. We acknowledge the assistance of Dr. I. Emanuel, of Nancy Mostoller, R.N., of Harry Dunning of the Seattle-King County Health Department, and of many King County Hospitals.
REFERENCES 1. Emanuel, I., Culver, B. H., Erickson, J. D., et al.: The further epidemiological differentiation of cleft lip and palate. A population study of clefts in King County, Washington, 1956-1965, Teratology 7: 271, 1973.
Instant screening for bacteriuria in children: Analysis of a dipstick Martin F. Randolph, M.D., F.A.A.P., F.A.A.A.S.,* and Kathleen Morris, M.T. (A.S.C.P.), Danbury, Conn.
BACTERIURIA can be demonstrated directly in the freshly voided urine specimen by quantitative culture 1,2 or indirectly by tests based on bacterial metabolism. 35 The latter are less intricate than the conventional culture and lend themselves better to office and to mass population screening programs. In recent studies the modified Greiss nitrite test, which is based upon the ability of most urinary pathogens to reduce nitrate to nitrite, identified 92 per cent of urine specimens containing more than 100,000 colonies per milliliter,4 with a false-positive rate of 7.6 per cent. 5 The reaction is dependent upon the ability of the Greiss reagent, an acid solution of alpha-naphthylamine and sulfanilic acid~ to rapidly develop a red color in the pres*Reprint address: 70 Deer Hill Ave., Danbury, Conn, 06810.
The Journal of Pediatrics february 1974
2. Miettienen, O. S.: Estimation of relative risk from individually matched series, Biometrics 26: 75, 1970. 3. Janz, D., and Fuchs, U.: Are antiepileptic drugs harmful when given during pregnancy? Ger. Med, Mon. 9: 20, 1964. 4. Lowe, C. R.: Congenital malformations among infants born to epileptic women, Lancet 1: 9, 1973. 5. German, J., Kowal, A., and Ehlers, K. H.: Trimethadione and human teratogenesis, Teratology 3: 349, 1970. 6. South, J.: Teratogenic effect of anticonvulsants, Lancet 2: 1154, 1972. 7. Spidel, B. D., and Meadow, S. R.: Maternal epilepsy and abnormalities of the fetus and newborn, Lancet 2: 839, 1972. 8. Melchior, J. C., Svensmark, O., and Trolle, D,: Placental transfer of phenobarbitone in epileptic women, and elimination in newborns, Lancet 2: 860, 1967. 9. Elshove, J., and Van Eck, J. H. M.: Aangeboren misvormingen, met name gespleten lip met of zonder gespleten verhemelte, bij kinderen van moeders met epilepsie, Ned. Tijdschr. Geneeskd. 115: 1371, 1971 10. Pashayan, H., Pruzansky, D., and Pruzansky, S.: Anticonvulsants teratogenic? Lancet 2: 702, 1971.
ence of even minute quantities of nitrite.4' 5 Recently, Warner-Chilcott Laboratories made available a simple paper dip test (Bac-U-Dip) based on the Greiss principle which gives an immediate reading relative to the presence or absence of bacteriuria. The present study was undertaken to further test the value of the instant nitrite test (Bac-U-Dip) as an indicator of bacteriuria in a large series of urine specimens. METHOD From October, 1972, until May, 1973, the school children in the third, fourth, and fifth grades of the Danbury School System were screened for covert bacteriuria. The parent was instructed to obtain a first morning urine specimen from the child at home in the cardboard container provided and to refrigerate the specimen promptly. The parents were not encouraged to cleanse the external genitalia, to spread the labia, nor to collect a midstream specimen. The child returned the specimen to his or her classroom; the school nurse collected a specimen from each student in the class and transported them to the office laboratory where they were refrigerated until processed the same morning. Each specimen was processed simultaneously by BacU-Dip and by quantitative culture. Bac-U-Dip strips were provided in amber bottles of 100, with instructions to keep refrigerated when not in use. A strip test was positive if the color registered pink within seconds after being dipped into the urine specimen; it was read as
Brief clinical and laboratory observations
Volume 84 Number 2
247
Table I. Bacteriuria: Detection by Bac-U-Dip and by colony count I
Sex
Namber patients
Bacteriuria, * Bacteriuria, Bac-U-Dip false neg. colony count dipstick
Transient Persistent I UTl by bacteriuria, bacteriuria, "~ dipstick, no. pts. no. pts. no. pts.
UT1 missed by dipstick
Male
1620
2
2
0
0
2
2
Female
1630
76
70
6
3
23
21
2
Total
3250
7.8
72
6
3
25
23
2
*Bacteriuria:more than 100,000 coloniesper millimeter. tPersistent bacteriuria:more than 100,000coloniesper millimeter in three consecutivespecimens.
negative if the strip failed to change color. Simultaneously a quantitative culture was done with the use of the loop-surface agar method on MacConkey media. 2 When specimens grew more than 10,000 colonies per milliliter of a single pathogen, subsequently collected specimens were retested at 12 or 24 hour intervals until bacteriuria was confirmed or excluded. RESULTS Voided specimens were collected on 3,250 children or approximately 90 per cent of children registered in the third, fourth, and fifth grades of the Danbury School System. With rare exceptions, all specimens collected were suitable for processing. Despite a simple collection technique by the parents at home, 97 per cent o f the specimens were sterile or contained fewer than 104 bacteria per milliliter, and fewer than 1" per cent o f the specimens grew out organisms in the range of 104 to 105 bacteria per milliliter. The total viable count exceeded 105 in 78 specimens (2.2 per cen0; these 78 specimens were from 28 patients; 25 patients had true bacteriuria, the total count exceeding 105 of a single pathogen in three consecutive specimens. In the remaining three patients, bacteriuria failed to persist and the bacteriuria was regarded as transient. BAC-U-DIP
ANALYSIS
Of 3,494 specimens, 79 (2.2 per cent) were Bac-U-Dip positive and 3,415 (97.8 per cent) were Bac-U-Dip negative; 3,394 voided specimens grew out fewer than 104 colonies and were uniformly Bac-U-Dip negative. Of 22 specimens in the 104 to 105 colonies per milliliter range, seven were Bac-U-Dip positive and 15 were negative. Thus the Bac-U-Dip response in this colony range appears to be variable. In the range of 105 to 106 however, of 78 specimens, 72 were identified as true positives and six were falsely negative. It follows that the correlation
of Bac-U-Dip positive specimens with colony counts exceeding 100,000 colonies per milliliter is 94 per cent (72/78); the correlation with Bac-U-Dip negative specimens is 93 per cent (6/78). Organisms isolated were identified by colony morphology only. The infecting organism in 82 per cent o f cases was E. coli; Klebsiella and Proteus were identified in approximately 8 and 3 per cent of cases, respectively. Of 3,415 specimens that were Bac-U-Dip negative, six specimens were in the range o f significant bacteriuria and were regarded as falsely negative. Klebsiella organisms were isolated in four specimens; in two specimens, there was a mixed culture of E. coli and Klebsiella, with Klebsiella predominating. In each instance the organism c u l t u r e d was tested for its ability to reduce nitrate; all were good nitrate reducers. All six specimens were from two girls with megacystis syndrome. These two children are the only patients with confirmed urinary tract infection who were missed by Bac-U-Dip analysis. The falsely negative Bat-U-Dip might be explained by the prolonged bladder incubation time characteristic of the megacystis syndrome which would allow the reduction o f nitrate to progress beyond the nitrite stage. 7 DISCUSSION The true measure of the Bac-U-Dip is the number of children with urinary tract infection detected as well as the number of cases missed. In the final analysis, urinary tract infection would have been detected by the Bac-U-Dip analysis alone in 23 children and would have gone undetected in two children. These were the two girls with megacystis syndrome noted above (Table I). On the basis of this experience, we would recommend that in the examination of children for significant bacteriuria, the first specimen of urine voided in the morning be collected and refrigerated until brought to the ofrice or clinic. Bac-U-Dip positive specimens should be
248
Brief clinical and laboratory observations
followed by quantitative urine bacteriology. If the urine is Bac-U-Dip negative and the child asymptomatic, culture studies are not indicated, Children found to be symptomatic, however, with Bac-U-Dip negative reactions should continue to have quantitative urine cultures until significant bacteriuria is confirmed or excluded. The Bac-U-Dip is recommended as a screening device for the child presenting for routine care; it does not replace the quantitative culture in the diagnosis of asymptomatic bacteriuria. We are indebted to Robert M. Gabrielson, M.D., Medical Director of Warner-Chilcott Laboratories of Morris Plains, N. J., for supplying the Bac-U-Dip strips.
The Journal of Pediatrics February 1974
2. Randolph, M. F., Greenfield, M., and Creasy, J.: Ten-second urine culture and colony count, Am. J. Dis. Child. 108: 348, 1964. 3. Smith, I., and Schmidt, J.: Evaluation of three screening tests for patients with significant bacteriuria, J. A. M. A. 181: 159, 1962. 4. Czerwinski, A., et al.: Further evaluation of the Greiss test to detect significant bacteriuria, Am. J. Obstet. Gynecol. 110: 677, 1971. 5. Andelman, M., et al.: A "stick test" for detection of asymptomatic bacteriui'ia, J. Urol. 100: 100, 1968. 6. Jespersen, J., and Deutch, J.: The detection of significant bacteriuria, First Medical University Department, Acta Med. Scand. 175: 191, 1964. 7. Lie, J. T.: Evaluation of a nitrite test kit (Stat-tes0 for the detection of significant bacteriuria, J. Clin. Pathol. 21: 443, 1968.
REFERENCES 1. Kass, E. H.: Chemotherapeutic and antibiotic drugs in the management of infection of the urinary tract, Am. J. Med. 18: 764, 1955.
Chemical contamination of umbilical catheter blood samples by infusates Connie Urquhart, M.T. (A.S.C.P.),* Abner H. Levkoff, M.D., and Noel Brown, M.D., Charleston, S. C.
C AT HE T E R S placed in umbilical vessels for the admin-. istration of parenteral fluids are commonly used f o r periodic sampling of the neonate's blood. It is generally felt that the catheter can be satisfactorily cleared of the infusate by withdrawing a discard three times the catheter's volume, a 1 ml. discard for a No. 5 Argyle * catheter with a volume of 0.3 ml. The discard is usually returned to the patient. When a 10 per cent dextrose solution is being infused by catheter, however, the chances of chemically contaminating blood sampled for From the Department of Pediatrics, Medical University of South Carolina. 9Reprint address: Department of Pediatrics, Medical University of South Carolina, 80 Barre St. Charleston, S. C. 29401. "i'Aloe.Cat. No, MAR 1602-5.
its glucose content via the catheter is great since the concentration of glucose in the infusate may be 100 times that of the blood: 10,000 mg. per 100 ml. of infusate versus 100 mg. per 100 ml. of blood. Thus, 0.01 ml. of 10 per cent dextrose solution contaminating 1 ml. of blood sample would elevate the blood sugar concentration of the sample by 100 mg. per 100 ml. To evaluate the hazard of such chemical contamination, a study was performed which was designed to simulate blood sampling via a catheter infusing 10 per cent dextrose into an umbilical vessel. The findings of this study were then corroborated in several neonates receiving 10 per cent dextrose via an umbilical artery catheter. METHODS
In vitro technique: Sampling from blood flask by simulated umbilical artery infusion catheter vs. direct aspiration by syringe and needle. A No. 5 Argyle catheter attached to a drip set was filled with a 10 per cent dextrose solution. The catheter was then clamped 1 cm. from its proximal end; the remainder of the distal end of the catheter was carefully wiped and placed into a flask containing 10 ml. of fresh heparinized blood. The drip set was detached and a 1 ml. sample of the flask blood was obtained via the catheter after clearing it with a 1 ml. discard of flask blood. After refilling the catheter with the 10 per cent dextrose infusion, the same sampling procedure was performed after a 3 ml. discard. One syringe was used to withdraw the discard, a second