Volume 116 Number 2
Editorial correspondence
3 19
only one infant had a predominant biotype of S. epidermidis as defined by D'Angio et al. Our resultsmay reflect an endemic population of organisms in our NICU, whereas those of D'Angio et al. may be reflective of the development of an epidemic strain (or strains) of S. epidermidis in their NICU. Finally, D'Angio et al. found that slime-producing strains became more prevalent over time, but we isolated slime-positive strains at a fairly constant rate of about 50% over time. This finding might be attributed to our lower proportion of S. epidermidis isolates, because other species of coagulase-negative staphylococci are less likely than S. epidermidis to be slime producers. 3 In summary, our data are not consistent with the observation by D'Angio et al. that the combination of S. epidermidis, slime production, and multiple antibiotic resistance confers a selective advantage to coagulase-negative staphylococci for surface colonization of premature infants in an NICU environment. We do, however, agree with their recommendation that more attention be directed to investigating specific factors within the NICU environment that may influence selection for various characteristics of coagulase-negative staphylococci, including antibiotic administration, use of indwelling lines and tubes, and the presence of other flora that may compete to colonize infants in the NICU.
these differences with the Halls' results may reflect alternative study methods, factors inherent to the organism or environment, or, as likely, internursery differences in antibiotic use, invasive diagnostic and therapeutic measures, and resident flora. In addition, we did not examine any microbiotogic properties of other organisms, including coagulase-positive strains. With regard to the emergence of specific biotypes of S. epidermidis, 89% of our study infants developed a predominant biotype by ! week of age. Although each infant had a predominant biotype, these patterns differed among nurseries and shifted within each nursery over time. We acknowledge that these results differ from those of Hall & Hall, but we believe that these patterns are not reflective of the development of an epidemic strain. Moreover, our study was performed in two physically separate newborn intensive care units. Finally, we agree that species other than S. epidermidis are less likely to produce slime, which may account for the differences between our results and those of Hall.and Hall. We also note, however, that Hall et al.] in a previous article, identified slime-positive colonization as a significant risk factor for the development of invasive coagulase-negative staphylococcal disease. Future studies should help clarify these important issues and controversies.
Sue L. Hall, MD Department of Pediatrics Section of Neonatology Olive View Medical Center and University of California Los Angeles School of Medicine Sylmar and Los Angeles, CA 90024-1752
Mary Catherine Harris, MD Stephen Baumgart, MD Children's Hospital of Philadelphia Philadelphia, PA 19104
Robert T. Hall, MD Department of Pediatrics Chief Neonatology Children's Mercy Hospital University of Missouri-Kansas City School of Medicine Kansas Oty, MO 64108 REFERENCES
1. Hall SL, Riddell SW, Barnes WG, et al. Evaluation of coagulase-negative staphylococcal isolates from serial nasopharyngeal cultures of premature infants. Diagn Microbiol Infect Dis (in press). 2. Christensen GD, Simpson WA, Bisno AL, et al. Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces. Infect Immun 1982;37:318-26. 3. Ishak MA, Groschel DHM, Mandell GL, et al. Association of slime with pathogenicity of coagulase-negative staphylococci causing nosocomial septicemia. J Clin Microbiol 1985;22: 1025-9.
Reply To the Editor: w e appreciate the comments of Drs. Hall and Hall about surface colonization with coagulase-negative staphylococci,'and acknowledge that their data are different. In our study, by l week of life, all infants had pure growths of Staphylococcus epidermidis, which persisted through the 1-month study period. We agree that
REFERENCE
1. Halt SL, Hall RT, Barnes WG, RiddelI S. Colonization with slime-positive coagulase-negative staphylococci as a risk factor for invasive coagulase-negative staphylococci infections in neonates. J Perinatol 1988;8:215-21.
Solubility of calcium and phosphorus in parenterai nutrition solutions To the Editor: Occlusion of central venous catheters by fibrin or mineral precipitation is a significant problem in infants and children who require long-term parenteral nutrition. These patients require greater amounts of calcium and phosphorus than adults because bone mineralization occurs at a rapid rate. 1,2 Duffy et al. (J PEDIa'rR 1989;114:1002-4) presented results of a protocoi using 0.1N hydrochloride for management of catheters presumably occluded by calcium phosphate precipitates. The Figure, relating calcium plus phosphorus concentrations to the percentage of protein in the pareuteral nutrition solution, erroneously presents the concentration as measured in miltiequivalents per milliliter; we believe that the measurement should be in milliequivalents per liter. Because the solubility of calcium and phosphorus is dependent on pH and temperature in addition to mineral concentration, there is no definitive method of determining how much calcium and phosphorus can be added to a parenteral nutrition solution without risk of precipitation. ConsequentIy, any information regarding solubility of these two minerals is important. Because the Figure ineludes a line above which precipitation did not occur, it could be
320
Editorial correspondence
The Journal of Pediatrics February 1990
used by the clinician to determine maximum amounts of calcium and phosphorus that can be maintained in solution. This graph oversimplifies calcium and phosphorus solubility, which undoubtedly was affected by a variety of factors in addition to percentage of protein. The parenteral nutrition solutions used for these patients differed in dextrose concentration, protein source, and percentage of protein, all of which affect solution pH. Increasing dextrose concentration decreases solution pH; in this study, dextrose concentration ranged from 10% to 25%. Two amino acid products, TrophAmine and Travasol, with inherently different pH values, were used but were not differentiated in the Figure. In addition, the authors did not state whether Or not L-cysteine hydrochloride was added to the TrophAmine-based solutions. Because L-cysteine hydrochloride acidifies solutions, thereby enhancing calcium and phosphorus solubility, 3 its addition is an important consideration. Percentage of protein also affects pH but certainly is not the only factor influencing the final solution pH and, ultimately, calcium and phosphorus solubility. We believe that the hydrochloride protocol presented is important and will provide institutions with a basis for developing an institution-specific protocol for management of central venous catheter occlusion. However, we caution against the use of the Figure as a guideline for determining calcium and phosphorus solubility. Laureen A. Drwal, PharmD Emily B. Cochran, PharmD Richard A. Helms, PharmD Department of Clinical Pharmacy University of Tennessee, Memphis, and Le Bonheur Children's Medical Center Memphis, TN 38163 REFERENCES
1. Knight P J, Buchanan S, Clatworthy HW, Calcium and phosphate requirements of preterm infants who require prolonged hyperalimentation. JAMA 1980;243:1244-6.
2. Committee on Nutrition. Calcium requirements in infancy and childhood. Pediatrics 1978;62:826-34. ! 3. Fitzgerald KA, MacKay MW. Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing Aminosyn PF. Am J Hosp Pharm t987;44:1396-400.
Reply To the Editor." The comments of Drwal et al. are correct; there is an error in the Figure shown in the article, and the graphic representation of solubility is simplistic. The correct units of measurement for calcium and phosphorus on the x axis are milliequivalents per deciliter and not milliequivalents per milliliter. As we stated in our discussion, other factors such as pH and temperature also affect solubility, and these factors may explain why most of our precipitates occurred in total parenteral nutrition (TPN) solutions in which the values for calcium and phosphorus were well below the normal range for our curve. The aim of our article was to describe an effective method to treat mineral precipitates; we did not imply nor intend that our solubility curve should be used by others. In fact, we are in the process of generating a new set of curves for various TPN solutions that will take into account pH and duration of storage. The TPN solutions used at the time of the study were Travasol 10% and TrophAmine, without cysteine hydrochloride added. The pH ranges for both these solutions overlap; therefore the same solubility curve was used. We now add cysteine hydrochloride to the TrophAmine. Our further experience confirms that hydrochloride acid treatment is effective in dissolving mineral precipitates in central venous catheters, and we are pleased that the authors concede this point. Lynn F. Duffy, MD Department of Gastroenterology and Nutrition Children's Hospital National Medical Center Washington, DC 20010
CORRECTION In the article " C o n g e n i t a l Rubella S y n d r o m e Associated With Calcific Epiphyseal Stippling and Peroxisomal Dysfunction," by Pike et al., published in the J a n u a r y 1990 issue of THE JOURNAL, the value listed in T a b l e II (p. 92) for pipecolic acid in control subjects as 10 should be
Editorial correspondence
3 19
only one infant had a predominant biotype of S. epidermidis as defined by D'Angio et al. Our resultsmay reflect an endemic population of organisms in our NICU, whereas those of D'Angio et al. may be reflective of the development of an epidemic strain (or strains) of S. epidermidis in their NICU. Finally, D'Angio et al. found that slime-producing strains became more prevalent over time, but we isolated slime-positive strains at a fairly constant rate of about 50% over time. This finding might be attributed to our lower proportion of S. epidermidis isolates, because other species of coagulase-negative staphylococci are less likely than S. epidermidis to be slime producers. 3 In summary, our data are not consistent with the observation by D'Angio et al. that the combination of S. epidermidis, slime production, and multiple antibiotic resistance confers a selective advantage to coagulase-negative staphylococci for surface colonization of premature infants in an NICU environment. We do, however, agree with their recommendation that more attention be directed to investigating specific factors within the NICU environment that may influence selection for various characteristics of coagulase-negative staphylococci, including antibiotic administration, use of indwelling lines and tubes, and the presence of other flora that may compete to colonize infants in the NICU.
these differences with the Halls' results may reflect alternative study methods, factors inherent to the organism or environment, or, as likely, internursery differences in antibiotic use, invasive diagnostic and therapeutic measures, and resident flora. In addition, we did not examine any microbiotogic properties of other organisms, including coagulase-positive strains. With regard to the emergence of specific biotypes of S. epidermidis, 89% of our study infants developed a predominant biotype by ! week of age. Although each infant had a predominant biotype, these patterns differed among nurseries and shifted within each nursery over time. We acknowledge that these results differ from those of Hall & Hall, but we believe that these patterns are not reflective of the development of an epidemic strain. Moreover, our study was performed in two physically separate newborn intensive care units. Finally, we agree that species other than S. epidermidis are less likely to produce slime, which may account for the differences between our results and those of Hall.and Hall. We also note, however, that Hall et al.] in a previous article, identified slime-positive colonization as a significant risk factor for the development of invasive coagulase-negative staphylococcal disease. Future studies should help clarify these important issues and controversies.
Sue L. Hall, MD Department of Pediatrics Section of Neonatology Olive View Medical Center and University of California Los Angeles School of Medicine Sylmar and Los Angeles, CA 90024-1752
Mary Catherine Harris, MD Stephen Baumgart, MD Children's Hospital of Philadelphia Philadelphia, PA 19104
Robert T. Hall, MD Department of Pediatrics Chief Neonatology Children's Mercy Hospital University of Missouri-Kansas City School of Medicine Kansas Oty, MO 64108 REFERENCES
1. Hall SL, Riddell SW, Barnes WG, et al. Evaluation of coagulase-negative staphylococcal isolates from serial nasopharyngeal cultures of premature infants. Diagn Microbiol Infect Dis (in press). 2. Christensen GD, Simpson WA, Bisno AL, et al. Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces. Infect Immun 1982;37:318-26. 3. Ishak MA, Groschel DHM, Mandell GL, et al. Association of slime with pathogenicity of coagulase-negative staphylococci causing nosocomial septicemia. J Clin Microbiol 1985;22: 1025-9.
Reply To the Editor: w e appreciate the comments of Drs. Hall and Hall about surface colonization with coagulase-negative staphylococci,'and acknowledge that their data are different. In our study, by l week of life, all infants had pure growths of Staphylococcus epidermidis, which persisted through the 1-month study period. We agree that
REFERENCE
1. Halt SL, Hall RT, Barnes WG, RiddelI S. Colonization with slime-positive coagulase-negative staphylococci as a risk factor for invasive coagulase-negative staphylococci infections in neonates. J Perinatol 1988;8:215-21.
Solubility of calcium and phosphorus in parenterai nutrition solutions To the Editor: Occlusion of central venous catheters by fibrin or mineral precipitation is a significant problem in infants and children who require long-term parenteral nutrition. These patients require greater amounts of calcium and phosphorus than adults because bone mineralization occurs at a rapid rate. 1,2 Duffy et al. (J PEDIa'rR 1989;114:1002-4) presented results of a protocoi using 0.1N hydrochloride for management of catheters presumably occluded by calcium phosphate precipitates. The Figure, relating calcium plus phosphorus concentrations to the percentage of protein in the pareuteral nutrition solution, erroneously presents the concentration as measured in miltiequivalents per milliliter; we believe that the measurement should be in milliequivalents per liter. Because the solubility of calcium and phosphorus is dependent on pH and temperature in addition to mineral concentration, there is no definitive method of determining how much calcium and phosphorus can be added to a parenteral nutrition solution without risk of precipitation. ConsequentIy, any information regarding solubility of these two minerals is important. Because the Figure ineludes a line above which precipitation did not occur, it could be
320
Editorial correspondence
The Journal of Pediatrics February 1990
used by the clinician to determine maximum amounts of calcium and phosphorus that can be maintained in solution. This graph oversimplifies calcium and phosphorus solubility, which undoubtedly was affected by a variety of factors in addition to percentage of protein. The parenteral nutrition solutions used for these patients differed in dextrose concentration, protein source, and percentage of protein, all of which affect solution pH. Increasing dextrose concentration decreases solution pH; in this study, dextrose concentration ranged from 10% to 25%. Two amino acid products, TrophAmine and Travasol, with inherently different pH values, were used but were not differentiated in the Figure. In addition, the authors did not state whether Or not L-cysteine hydrochloride was added to the TrophAmine-based solutions. Because L-cysteine hydrochloride acidifies solutions, thereby enhancing calcium and phosphorus solubility, 3 its addition is an important consideration. Percentage of protein also affects pH but certainly is not the only factor influencing the final solution pH and, ultimately, calcium and phosphorus solubility. We believe that the hydrochloride protocol presented is important and will provide institutions with a basis for developing an institution-specific protocol for management of central venous catheter occlusion. However, we caution against the use of the Figure as a guideline for determining calcium and phosphorus solubility. Laureen A. Drwal, PharmD Emily B. Cochran, PharmD Richard A. Helms, PharmD Department of Clinical Pharmacy University of Tennessee, Memphis, and Le Bonheur Children's Medical Center Memphis, TN 38163 REFERENCES
1. Knight P J, Buchanan S, Clatworthy HW, Calcium and phosphate requirements of preterm infants who require prolonged hyperalimentation. JAMA 1980;243:1244-6.
2. Committee on Nutrition. Calcium requirements in infancy and childhood. Pediatrics 1978;62:826-34. ! 3. Fitzgerald KA, MacKay MW. Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing Aminosyn PF. Am J Hosp Pharm t987;44:1396-400.
Reply To the Editor." The comments of Drwal et al. are correct; there is an error in the Figure shown in the article, and the graphic representation of solubility is simplistic. The correct units of measurement for calcium and phosphorus on the x axis are milliequivalents per deciliter and not milliequivalents per milliliter. As we stated in our discussion, other factors such as pH and temperature also affect solubility, and these factors may explain why most of our precipitates occurred in total parenteral nutrition (TPN) solutions in which the values for calcium and phosphorus were well below the normal range for our curve. The aim of our article was to describe an effective method to treat mineral precipitates; we did not imply nor intend that our solubility curve should be used by others. In fact, we are in the process of generating a new set of curves for various TPN solutions that will take into account pH and duration of storage. The TPN solutions used at the time of the study were Travasol 10% and TrophAmine, without cysteine hydrochloride added. The pH ranges for both these solutions overlap; therefore the same solubility curve was used. We now add cysteine hydrochloride to the TrophAmine. Our further experience confirms that hydrochloride acid treatment is effective in dissolving mineral precipitates in central venous catheters, and we are pleased that the authors concede this point. Lynn F. Duffy, MD Department of Gastroenterology and Nutrition Children's Hospital National Medical Center Washington, DC 20010
CORRECTION In the article " C o n g e n i t a l Rubella S y n d r o m e Associated With Calcific Epiphyseal Stippling and Peroxisomal Dysfunction," by Pike et al., published in the J a n u a r y 1990 issue of THE JOURNAL, the value listed in T a b l e II (p. 92) for pipecolic acid in control subjects as 10 should be
