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Interference by third-generation cephalosporins with neonatal screening for galactosemia
EDITORIAL CORRESPONDENCE
Interference by third-generation cephalosporins with neonatal
REFERENCE
1.
screening for galactosemia To the Editor." The report by Clemens et al. (J PEDIATR 1986;109:713-4) regarding interference by antibiotics in the Guthrie bacterial inhibition assay for galactosemia screening prompts us to report similar observations. Between April and September 1985, the Oregon State Public Health Laboratory observed a threefold increase in the number of newborn screening samples in which the galaetose level was apparently elevated. No abnormal elevations were seen in bacterial inhibition assays for phenylalanine, methionine (Bacillus subtilis ATCC 6633), tyrosine, or leucine (B. subtilis ATCC 6051) on the same samples. The galactose assay was based on an auxotroph of Eseherichia coli W5 in which galactose inhibits bacterial growth but galactose-l-phosphage does not. Samples were not autoclaved before analysis. Retrospective analysis of all infants with positive test results during this period indicated that most infants were receiving antibiotics: ceftriaxone--nine infants; cefotaxime--five; tobramycin and cefotaxime--one; no antibiotlcs--two. After discontinuation of antibiotics, infants had normal screening test results. Therefore we obtained serum prospectively from seven children (6 months to 4 years of age) and four newborn infants receiving antibiotic therapy to test for antibiotic interference. Serum from four children receiving ceftriaxone gave abnormal results. Serum from three children receiving cefotaxime (drawn 5 to 6 hours after dosing) and four neonates receiving ampicillin and gentamicin yielded normal results. The E. coli W5 auxotroph was inhibited by 0.025 #g/ml of ceftriaxone or cefotaxime, a concentration well exceeded during therapy. If the galactose screening test and the Beutler enzyme test for galactose-l-phosphate uridyl transferase activity show an abnormal result, the diagnosis of galactosemia is presumed and immediate action is initiated. As a result of these studies, however, all samples with an abnormal galactose result are retested with E. coli, which is not sensitive to galactose, but its growth is inhibited by antibiotics. In either case, the sample is considered abnormal until another sample has been tested. A fluorometric assay for galactose and galactose-l-phosphate~ that is not affected by antibiotics should reduce the recall rate for galactosemia screening and will be implemented soon. Jack P. Schunk, MD John S. Bradley, MD Neil R.M. Buist, MD, ChB, FRCPE Department o f Pediatrics Oregon Health Sciences University Portland, OR 97201 Michael R. Skeels, PhD, M P H Oregon State Public Health Laboratory Portland, OR 97201
842
Misuma H, Wada H, Kawakami M, Ninomiya H, Shohmoci T. Galactose and galactose-l-phosphate spot test for galactosemia screening. Clin Chim Acta 1981; 111:27-32.
Reply To the Editor: Schunk et al. retested all samples with an abnormal galactose result using an E. coli that is not sensitive to galactose but that is inhibited in its growth by antibiotics. We think that this procedure could be of theoretical interest but is not of practical usefulness. It requires another 24 hours, and if there is an abnormal result in this second procedure, this indicates only that there is an influence of antibiotics but does not exclude the possibility that the infant could have galactosemia. Antibiotic therapy in neonates with galactosemia is very common because of their disposition for sepsis. ~ Thus even in case of antibiotic interference, another sample has to be tested, as Schunk et al. point out. Schunk et al. furthermore report that they will implement a fluorometric assay that is not affected by antibiotics. We already have implemented an analogous procedure that we hope to publish within the next few months. Peter C. Clemens, MD Christel Plettner, ScD Department o f Pediatrics University o f Hamburg Martinistrasse 52 D-2000 Hamburg 20 Federal Republic o f Germany REFERENCE
1.
Levy HL, Sepe S J, Shih VE, Vawter GF, Klein JO. Sepsis due to Escherichia coli in neonates with galactosemia. N Engl J Med 1977;297:823-5.
Intravenous immunoglobulin for neonatal alloimmune
thrombocytopenia To the Editor: The article by Massey et al. (J PEDIATRICS 1987;111:133-5) concludes that intravenous immunoglobulin (IVIG) is efficacious in reversing the thrombocytopenia of neonatal isoimmunization. The authors also state that "because it may take up to 24 hours for the platelet count to reach a 'safe' level, it is still.advisable that maternal platelets be available in the event of life-threatening bleeding in the infant." I wish to caution against acceptance of IVIG as first-choice therapy for infants with neonatal alloimmune
Interference by third-generation cephalosporins with neonatal
REFERENCE
1.
screening for galactosemia To the Editor." The report by Clemens et al. (J PEDIATR 1986;109:713-4) regarding interference by antibiotics in the Guthrie bacterial inhibition assay for galactosemia screening prompts us to report similar observations. Between April and September 1985, the Oregon State Public Health Laboratory observed a threefold increase in the number of newborn screening samples in which the galaetose level was apparently elevated. No abnormal elevations were seen in bacterial inhibition assays for phenylalanine, methionine (Bacillus subtilis ATCC 6633), tyrosine, or leucine (B. subtilis ATCC 6051) on the same samples. The galactose assay was based on an auxotroph of Eseherichia coli W5 in which galactose inhibits bacterial growth but galactose-l-phosphage does not. Samples were not autoclaved before analysis. Retrospective analysis of all infants with positive test results during this period indicated that most infants were receiving antibiotics: ceftriaxone--nine infants; cefotaxime--five; tobramycin and cefotaxime--one; no antibiotlcs--two. After discontinuation of antibiotics, infants had normal screening test results. Therefore we obtained serum prospectively from seven children (6 months to 4 years of age) and four newborn infants receiving antibiotic therapy to test for antibiotic interference. Serum from four children receiving ceftriaxone gave abnormal results. Serum from three children receiving cefotaxime (drawn 5 to 6 hours after dosing) and four neonates receiving ampicillin and gentamicin yielded normal results. The E. coli W5 auxotroph was inhibited by 0.025 #g/ml of ceftriaxone or cefotaxime, a concentration well exceeded during therapy. If the galactose screening test and the Beutler enzyme test for galactose-l-phosphate uridyl transferase activity show an abnormal result, the diagnosis of galactosemia is presumed and immediate action is initiated. As a result of these studies, however, all samples with an abnormal galactose result are retested with E. coli, which is not sensitive to galactose, but its growth is inhibited by antibiotics. In either case, the sample is considered abnormal until another sample has been tested. A fluorometric assay for galactose and galactose-l-phosphate~ that is not affected by antibiotics should reduce the recall rate for galactosemia screening and will be implemented soon. Jack P. Schunk, MD John S. Bradley, MD Neil R.M. Buist, MD, ChB, FRCPE Department o f Pediatrics Oregon Health Sciences University Portland, OR 97201 Michael R. Skeels, PhD, M P H Oregon State Public Health Laboratory Portland, OR 97201
842
Misuma H, Wada H, Kawakami M, Ninomiya H, Shohmoci T. Galactose and galactose-l-phosphate spot test for galactosemia screening. Clin Chim Acta 1981; 111:27-32.
Reply To the Editor: Schunk et al. retested all samples with an abnormal galactose result using an E. coli that is not sensitive to galactose but that is inhibited in its growth by antibiotics. We think that this procedure could be of theoretical interest but is not of practical usefulness. It requires another 24 hours, and if there is an abnormal result in this second procedure, this indicates only that there is an influence of antibiotics but does not exclude the possibility that the infant could have galactosemia. Antibiotic therapy in neonates with galactosemia is very common because of their disposition for sepsis. ~ Thus even in case of antibiotic interference, another sample has to be tested, as Schunk et al. point out. Schunk et al. furthermore report that they will implement a fluorometric assay that is not affected by antibiotics. We already have implemented an analogous procedure that we hope to publish within the next few months. Peter C. Clemens, MD Christel Plettner, ScD Department o f Pediatrics University o f Hamburg Martinistrasse 52 D-2000 Hamburg 20 Federal Republic o f Germany REFERENCE
1.
Levy HL, Sepe S J, Shih VE, Vawter GF, Klein JO. Sepsis due to Escherichia coli in neonates with galactosemia. N Engl J Med 1977;297:823-5.
Intravenous immunoglobulin for neonatal alloimmune
thrombocytopenia To the Editor: The article by Massey et al. (J PEDIATRICS 1987;111:133-5) concludes that intravenous immunoglobulin (IVIG) is efficacious in reversing the thrombocytopenia of neonatal isoimmunization. The authors also state that "because it may take up to 24 hours for the platelet count to reach a 'safe' level, it is still.advisable that maternal platelets be available in the event of life-threatening bleeding in the infant." I wish to caution against acceptance of IVIG as first-choice therapy for infants with neonatal alloimmune