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Outbreak of Candida bloodstream infections associated with retrograde medication administration in a neonatal intensive care unit
Outbreak of Candida bloodstream infections associated with retrograde medication administration in a neonatal intensive care unit R o b e r t J. Sherertz, MD, K a t e S. Gledhill, RN, K e n n e t h D. H a m p t o n , BS, M i c h a e l A. Pfaller, MD,* L a u r e n c e B. G i v n e r , MD, Jon S. A b r a m s o n , MD, a n d R o b e r t G. Dillard, MD From the Department of Infection Control and Hospital Epidemiology, North Carolina Baptist Hospital, the Section on Infectious Diseases, Departments of Medicine, and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, and the Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa An o u t b r e a k of c a n d i d e m i a i n v o l v i n g f i v e infants r e c e i v i n g t o t a l p a r e n t e r a l nutrition in the n e o n a t a l intensive c a r e unit was i n v e s t i g a t e d . Cultures of the intrav e n o u s fluids d e m o n s t r a t e d that the r e t r o g r a d e m e d i c a t i o n syringe fluids were s i g n i f i c a n t l y more likely to be c o n t a m i n a t e d with C a n d i d a than were other fluids b e i n g a d m i n i s t e r e d to the infants (p <0.001). C a n d i d e m i a was s i g n i f i c a n t l y a s s o c i a t e d with t o t a l p a r e n t e r a l nutrition (p = 0.04) and r e t r o g r a d e m e d i c a t i o n a d m i n i s t r a t i o n (p = 0.02). A survey of nursing p r a c t i c e found that reuse of the r e t r o g r a d e syringes was the most l i k e l y cause of c o n t a m i n a t i o n . M o l e c u l a r typing showed that the strains of C a n d i d a a l b i c a n s that were i s o l a t e d from the b l o o d s t r e a m were also found in the r e t r o g r a d e syringes and that at least three strains of C. a l b i c a n s and one strain e a c h of C a n d i d a tropicalis a n d C a n d i d a parapsilosis were i n v o l v e d . In vitro growth curves d e m o n s t r a t e d that C a n d i d a s p e c i e s had a s e l e c t i v e growth a d v a n t a g e versus b a c t e r i a in the t o t a l parenteral nutrition fluid. An in vitro s i m u l a t i o n of the r e t r o g r a d e m e d i c a t i o n administration system suggested that the o u t b r e a k p r o b a b l y d e v e l o p e d after the f r e q u e n c y of c h a n g i n g intravenous tubing was d e c r e a s e d from e v e r y 24 hours to e v e r y 72 hours. The o u t b r e a k was t e r m i n a t e d by using syringes o n l y o n c e a n d resuming intravenous tubing c h a n g e s e v e r y 24 hours. Retrograde m e d i c a t i o n a d m i n i s t r a t i o n in a s s o c i a t i o n with t o t a l p a r e n t e r a l nutrition m a y increase the risk of C a n d i d a line infection. (J PEDIATR1992;120:455-61)
Outbreaks of Candida bloodstream infection have been associated with total parenteral nutrition] -5 pressure moni-
Presented in part at the Third International Conference on Nosocomial Infections, August 1990, Atlanta, Ga., and the Society for Pediatric Research, April 199l, New Orleans, La. Submitted for publication July 25," 199l; accepted Oct. 3, 1991. Reprint requests: Robert J. Sherertz, MD, Section on Infectious Diseases, Department of Medicine, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27103. *Now at the Department of Pathology, Oregon Health Sciences University, Portland, Oregon. 9/23/34172
tors, 3,4 and intravenous additives. 1,2,s In half of the reported outbreaks the source of Candida could not be identified, 6-~~possibly because of the lack of readily available and reliable typing methods for Candida. 5, II We re-
CFU NICU TPN
Colony-forming units Neonatal intensive care unit Total parenteral nutrition
cently evaluated an outbreak of Candida bloodstream infections in a neonatal intensive care unit. Our investigation and successful intervention are summarized in this report. 455
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Fig. 1. Time course of Candida bloodstreaminfection in fiveinfants in NICU. Each symbolwith a Candida species label represents a blood culture positivefor that species on that day, except for those marked with arrows, which are catheter-tip cultures~ First positive blood culture was documented on Jan. 2, 1990; last was documented on Feb. 5, 1990. OUTBREAK SUMMARY In January 1990, five infants in an NICU had Candida bloodstream infections (Fig. 1). Two of the infants died of Candida infection despite therapy with amphotericin B. The five infants weighed 1400 + 700 gm (mean _+ SD), averaged 31 _+ 6 weeks of gestational age at birth, and had been hospitalized for 35 _+ 22 days at the time of Candida infection. Each infant had a patent ductus arteriosus (four of the five requiring surgical repair) and were receiving antibiotics and TPN before and during Candida infection. The attack rate for candidemia during the outbreak period (5.9%; 5/85 infants), was eight times greater than the attack rate seen in the previous year (0.7%; 4/539 infants). The outbreak began 2 months after the frequency of intravenous line changes was decreased from every 24 hour to every 72 hours. The five infants acquired candidemia in three of the four wards in the NICU. Three of the infants (patients 2, 3, and 4) had infections in one ward within 5 days of one another. The outbreak was first recognized on the day that patient 3 died (Fig. 1, day 22). At that time efforts to minimize cross infection were undertaken: (1) the use of gloves for all infant contacts was initiated, (2) chlorhexidine was selected as the standard hand-washing agent and foot-operated dispensers were installed, (3) all infected and exposed infants were placed in a single ward, and (4) the wearing of gowns was required for persons holding infants. Routine infection control practices were emphasized. All NICU and pharmacy personnel were examined for evidence of hand
dermatitis; none was found. At the same time a search was initiated for a Candida albicans reservoir (as described in the Methods section). During the next 9 days, patient 2 died and the first culture of retrograde syringe fluid grew C. albicans. The retrograde medication system (Fig. 2) was designed to allow administration through a single line of medications (such as antibiotics) that are generally incompatible with TPN fluid, to minimize the total volume given to each infant. 12, 13 As a result of the retrograde fluid culture results, a second series of interventions was carried out. On day 31, all 23 infants in the NICU had their intravenous tubing and catheters changed. The then-current practice of changing tubes every 72 hours was returned to every 24 hours. In additon, the recommendation was made that all retrograde syringes be used only once, and a nursing practice survey was initiated to determine how these syringes were actually being used. No new cases occurred after that time, and the outbreak was considered to have ended on day 35. METHODS Environmentalreservoir cultures. Three different types of solutions were cultured during the last 2 weeks of the outbreak: (1) any lotion, soap, or other such substance that could come in contact with either an infant's skin or the hands of any personnel; (2) barrier syringe solution (10% glucose) prepared by the pharmacy; (3) in-line fluids at the time that intravenous tubing was changed. Cultures were prepared by surface plating 0.1 ml of each solution onto
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Candida outbreak in a neonatal I C U
TPN Fluid
Other Fluids
Waste Syringe
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Flush Syringe
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Fig. 2. Retrograde medication administration system. Diagram of locations where various fluid bags and syringes insert
into intravenous tubing. Distances (in inches) at bottom of figure indicate |engths of different segments of tubing. Numbers at top of figure show frequency of Candida species isolation from fluid being sampled. All isolates but one were C. albieans: the other was C. tr~piealis (barrier syringe).
Columbia blood agar plates (Carr-Scarborough Microbiologicals, Inc.. Stone Mountain. Ga.) and inoculating t ml of each solution into l0 ml of trypticase soy.broth (TSB: Becton Dickinson Microbiology Systems. Cockeysville. Md ). Plates and broths were incubated at 37 ~ C for 72 hours, and each broth was also subcultured onto a blood agar plate and incubated for an additional 72 hours. In vitro retrograde administration simulation. Retrograde medication administration was performed in our NICU by means of the components outlined in Fig. 2. The clamps below the barrier syringe and above the waste syringe were closed, isolating the waste and barrier syringes connected by 170 inches (432 cm) of tubing. Then 1 ml 10% glucose solution from the barrier syringe was injected retrogradely into the line: this was followed by injection of the medication and then an additional l ml 10% glucose solution into the same port. The syringe line segments were clamped off. the line clamps were opened, and the medication was pumped in, with the 10% glucose solution barriers above and below separating it from the TPN fluid. We simulated the retrograde administration system in our laboratory by using identical components, as diagramed in Fig. 2, except that the bags marked "'other fluids" and "Intralipid" were not present and the tubing was connected to a urine drainage bag. The TPN fluid used. which was the same as that given to the infants in the neonatal ICU. consisted of the following: 250 ml crystalline amino acid solution (Aminosyn; Abbott Laboratories), 179 m170% glucose solution (Abbott), 54 ml sterile water for injection (Ab-
bott), l0 ml multiple electrolyte concentrate (Lypholyte II; Lyphomed), 5 ml multivitamin preparation (M.V.I. Pediatric; Armour), 2 ml sodium phosphates (Lyphomed), and 1 ml trace element preparation (Pedtrace-4; Lyphomed). All components (except for the needle) were changed at either 24-, 48-, or 72-hour intervals. Retrograde administration of antibiotics was simulated by using 10% glucose as the barrier solution and phosphate-buffered saline solution in place of the antibiotic solution. Waste syringes and barrier syringes were used only once. Simulated medication was given twice in 24 hours (at 9 AM and 4 PM). Each simulated retrograde system was inoculated with C. albicans (blood culture isolate from patient 2; Fig. 1) at the start of the trial. A sterile swab dipped into phosphatebuffered saline solution containing 102 C F U / m l was used to contaminate the tip of the barrier 'syringe. Quantitative cultures from the barrier-syringe port and the flush-syringe port were obtained just before simulated medication administration. Each sample and a i:I00 dilution in phosphate-buffered saline solution were surface plated (0.1 ml) onto blood agar plates and incubated at 37 ~ C for 48 hours. Each simulated retrograde system was allowed to run for 90 hours; then material from the lumen of the 20-gauge needle was quantitatively cultured by flushing the lumen three times with 3 ml trypticase soy broth and surface plating the recovered solution as previously described. Growth curves. Three different strains of Candida isolated from patients in the NICU (two C. albicans and one Candidaparapsilosis), five gram-negative bacilli, and two Staphy-
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The Journal of Pediatrics March 1992
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means of an ultraviolet transilluminator and Polaroid 107C film (Polaroid Corp. Medical Products, Cambridge, Mass). Southern hydridization. Southern hybridization analysis (of C. albicans isolates only) was performed as described previously. 14The DNA probe used was 27A, a species-specific DNA probe constructed from a dispersed, repeated DNA segment from the C. albicans genome, ~5 as provided by Dr. Stewart Scherer (University of Minnesota School of Medicine, Minneapolis, Minn.). Hybridization was performed at 68 ~ C. Low-stringencY washings were performed with saline citrate at twice standard strength and 0.2% sodium dodecyl sulfate at 55 ~ C. Autoradiography was performed at - 7 0 ~ C for 30 minutes with Kodak XOMATAR film (Eastman Kodak Co., Rochester, N.Y.). Statistical analysis. All statistical comparisons of proportions had at least one expected cell size of less than 5. Therefore a two-tailed Fisher Exact Test was used for each comparison. Quantitative culture results were compared with the Mann-Whitney rank-sum test. RESULTS
. 0
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+
at
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Fig. 3. Results of contaminating simulated retrograde medication administration system with C. albicans. Barrier port was contaminated initially, and various sites were sampled at intervals shown. A, Tubing changed every 24 hours (n = 8); B, Tubing changed every 48 hours (n = 8); C, Tubing changed every 72 hours (n = 4). Bars represent SEM. Where bars are not shown, they were smaller in size than symbol used.
Iococcus species were grown in TPN fluid, 10% glucose, and intravenous lipid emulsion (Intralipid; KabiVitrum) for 96 hours at 22 ~ C. Quantitative cultures, with dilutions and surface plating on blood agar, were prepared once or twice daily. Typing of Candida albicans strains. Ten strains of C. albicans and two strains of C. parapsilosis isolated from the patients or intravenous fluids during the outbreak investigation were sent to the Special Microbiology Laboratory at the University of Iowa (M. A. P.) for DNA typing. Each strain was identified only by a number so that the typing laboratory would be unaware of any clinical or epidemiologic associations. Restriction-endonuclease analysis o f chromosomal DNA. Stored isolates of C. albicans and C. parapsilosis were plated on Sabouraud dextrose agar and incubated at 30 ~ C for 16 hours. Chromosomal DNA was isolated and separate samples were subjected to restriction-endonuclease digestion with EcoRI and BstNI, as described previously. 14 The restriction fragments were separated by electr0Phoresis at 45 V for 16 hours on 0.7% agarose gels containing ethidium bromide. Markers for molecular weight were included in each gel. Gels were photographed by
Environmental reservoir cultures. Ninety cultures were performed on topically used solutions, including baby Soap (26 samples), hand lotion (18 samples), ointment (11 sampies), Hibiclens (Stuart Pharmaceuticals, Wilmington, Del.) hand-washing agent (10 samples), Detachal adhesive remover (Ferndale Laboratories, Inc., Ferndale, Mich. (9 samples), and miscellaneous other solutions (16 samples). All cultures of topical solutions were negative for yeasts and bacteria. No neutralization or filtration was done with antiseptic solutions; it therefore cannot be said with certainty that these solutions were not contaminated. Cultures of 38 samples of barrier solution (10% glucose) prepared by the pharmacy were negative for yeasts and bacteria. Fluid from barrier syringes and waste syringes used for retrograde medication administration (11 /267, 4.1%) were more likely to grow Candida (Fig. 2) than the other fluids sampled (1/339, 0.3%; p <0.001, Fisher Exact Test). Ten C. albicans strains were isolated from the retrograde syringe fluid, and each grew in quantities ~>50,000 C F U / m l in solution. One additional culture from a retrograde syringe grew C. parapsilosis and several syringes grew different bacteria in small numbers (<1000 CFU/ml). In vitro retrograde administration simulation. All barrier syringes were contaminated with C. albicans when sampled for culture 17 hours after inoculation (Fig. 3). Progressively higher counts of C. albicans were found in fluid aspirated through both the barrier port and the flush port at each time interval until the tubing was changed. All subsequent in-line cultures were negative for pathogens. Catheter lumina were significantly less likely to be contaminated with C. albicans if intravenous tubing was changed every 24 hours (0/8) than if it was changed every 48 hours (6/8) or every 72 hours (4/4) (p <0.006, Fisher Exact Test).
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Growth curves. Of the three different nutrient-containing fluids (10% glucose, TPN solution, and Intralipid) that were given to infants, in the NICU, only the TPN solution offered a selective growth advantage to Candida at room temperature (Fig. 4). Data on the two gram-negative organisms not shown in Fig. 4 (Acinetobacter anitratus and Enterobacter agglomerans) were essentially identical to those on the other gram-negative bacteria. Nursing survey. A survey of 43 NICU nurses identified a number of practices with the potential for facilitating line contamination and cross infection. Forty-eight percent of respondents reused syringes until empty; the syringes were stored in the refrigerator between flushes. Direct observation revealed that a syringe labeled with one infant's name occasionally was found in a different infant's line. Less frequently (16%) staff members reported that syringes with residual 10% glucose were moved from the old line to the new line when intravenous tubing was changed. Forty-nine percent of respondents stated that waste syringes were emptied after being filled and then were reinserted into the waste port; in some cases it was not clear whether waste syringes were ever discarded. Two answers were given by the nurses to explain why they were reusing the syringes. The first reason was that the nurses had been trained to perform this technique by another nurse; this practice had been going on for at least several months. The second reason was that the nurses were trying to save money by using all of the 10% glucose solution. In addition, there was a decrease in the nurse/infant staffing ratio during the outbreak period in comparison with that during the previous 12 months (3.0 vs 3.5, Nursing Productivity and Quality Software; Medicus Systems Corp., Evanston, Ill.). East Coast NICUs (level III) were surveyed regarding whether they used the retrograde method of medication administration; 7 of 12 were using the method. Candida typing. The DNA typing was carried out with 10 strains of C. albicans and two strains of C. parapsilosis isolated during the outbreak investigation (Fig. 5). All patient isolates that could be retrieved from the clinical microbiology laboratory and all isolates from our outbreak investigation were typed. All isolates of C. albicans from patients 1 (urine, lane 2), 2 (bloodstream, lane 3; retrograde syringe, lane 10), and 4 (bloodstream, lane 4; retrograde syringes, lanes 6, 7, and 9) had identical DNA-fragment profiles (type A) after digestion with EcoRI and BstNI, suggesting transmission of this strain from one patient to another. Distinctly different DNA restriction-fragment profiles were observed for a. bloodstream isolate from patient 3 (type B, lane 1), a syringe isolate from an uninfected infant (type C, lane 5), and an isolate from a 10% glucose solution from another uninfected infant (type D, lane 8). The two C. parapsilosis isolates from patient 5 had identical DNA restriction fragment profiles a n d were different from the C. albicans strains.
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Fi9. 4. Growth curves of eight different organisms in three solutions infused into infants in NICU. Each point is mean of two samples done in parallel. A, Dextrose (10%). B, Intravenous lipid emulsion (Intralipid). C, TPN fluid. Symbols: A, C. albicans (see Fig. l, patient 4, January 22); 0, C. albicans, noncase patient; II, C. parapsilosis (see Fig. 1, patient 5, January 21); A, Escherichia coli; O, Enterobacter aerogenes; [~, Klebsiella pneumoniae; V, Staphylococcus aureus; O, Staphylococcus epidermidis; solid line, Candida; dashed line, Gram-negativebacteria; dashed-dotted line, staphylococci.
Correlation of TPN and retrograde medication administration with candidemia. During the outbreak, infants receiving TPN (40/85; 47.1%) or TPN plus retrograde medications (36/40) were more likely to have candidemia than infants Who did not receive these treatments (TPN, 5/40 vs 0/45, p = 0.04; TPN plus retrograde medications, 5/36 vs 0/49, p = 0.02). Within the subgroup who received TPN, infants with candidemia had more days of TPN (20.2 + 9.7 vs 10.6 _+ 8.7 days; p = 0.03) than did those without bloodstream infection (n = 34). Infants with candidemia had more days of retrograde medication (12.2 + 4.8 vs 6.2 + 7.3 days; p = 0.02) and a greater number of line breaks because of retrograde medication administration (74.0 + 40.3 vs 24.2 + 39.4; p = 0.004) than did infants without candidemia (n = 30).
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5. Southern hybridization autoradiography of 10 strains of C.~albicans after restriction-endonuclease digestion with EcoRI. DesignationsA, B, C, and D are distinct types based on band patterns. Origin of each strain is found in Results section.
DISCUSSION The incidence of nosocomial Candida infection, including outbreaks, has been increasing.11~ 16 The mechanisms for many outbreaks have not been identified.6-t~ The Candida outbreaks with identified mechanisms of transmission, including one NICU outbreak, 3 were caused by extrinsic contamination of intravenously administered medications or vascular-access apparatus. 15 The mechanism for the outbreak that we investigated falls into the latter category. In our NICU five infants apparently acquired Candida bloodstream infection as a result of contaminated retrograde medication syringes. Candida bloodstream infection Occurred only in infants receiving retrograde medications in association With TPN. Infants in the retrograde medication subgroup wh o acquired Candida bloodstream infection had the greatest number of line breaks into the retrograde system and therefore the greatest risk of line contamination. Retrograde medication syringes were more likely to be contaminated by Candida than were other fluid reservoirs attached to the intravenous tubing during the outbreak period. Finally, molecular typing demonstrated for two of the infants that the same strain of C. albicans was isolated botfi from the retrograde syringes and from the bloodstream. The Candida strains causing the outbreak were both clustered and multifocal in origin. The multifocal origin of the outbreak suggests a generalized predisposition toward infection by the genus Candida. Our in vitro growth curves
The Journal of Pediatrics March 1992
demonstrated that Candida species have a selective growth advantage in TPN fluid administered to the infants in our NICU but do not have this advantage with the Intralipid or 10% glucose solutions. One previous study suggested that protein hydrolysate solutions by themselves are selective for Candida rather than bacteria, whereas synthetic amino acid solutions are not) 7 A second study found that casein hydrolysate plus dextrose was not selective for Candida but that a synthetic amino acid solution plus dextrose was selective.tS Our TPN solution contained synthetic amino acids plus dextrose in addition to other additives; the contribution of the other additives to the selective growth of Candida is unknown. Although the retrograde syringes were initially contaminated, it was the TPN fluid that probably allowed selective replication of yeasts. The precipitating event for this outbreak may have been the reduction in the frequency with which intravenous tubing was changed, from every 24 hours to every 72 hours, in line with hospital policy. Current Centers for Disease Control recommendations state that it is safe to change intravenous tubing every 48 hours.r9 Although our outbreak was associated with suboptimal nursing practice that was possibly accentuated by a decrease in the nurse/infant ratio, our in vitro simulation suggests that the Centers for Disease Control recommendations may not be optimal for clinical settings where lines containing TPN solution must be opened repeatedly to administer therapy. The safest approach to the administration of TPN and incompatible intravenous medications to infants in the N I C U remains to be determined. With proper technique it may be feasible to safely change intravenous tubing in the retrograde system less frequently than every 24 hours: however, until data support this contention, it seems prudent to change intravenous tubing every 24 hours. Because of the high risk for contamination of the retrograde system by Candida and the finding that more than 50% of 12 East Coast level III NICUs used this method of medication administration, other NICUs should carefully examine their TPN administration practices to ensure safety. We greatly appreciate the technical skills of Richard Hollis. REFERENCES
1. Plouffe JF, Brown DG. Silva J Jr. Eck T. Stricof RL. Fekety R Jr. Nosocomialoutbreak of Candida parapsilosis fungemia related to intravenous infusions. Arch Intern Med 1977: 137:1686-9. 2. Solomon SL. Khabbaz RF. Parker RH. et al. An outbreak of Candida parapsilosis bloodstream infections in patients receiving parenteral nutrition. J Infect Dis 1984:149:98-102. 3. Solomon SL, Alexander H, Eley JW, et al. Nosocomial fungemaa in neonates associatedwith intravascular pressuremonitoring devices. Pediatr Infect Dis 1986:5:680-5. 4. Weems JJ JR, Chamberland ME, Ward J. Willy M, Padhye AA. Solomon SL. Candida parapsilosis fungemla associated with parenteral nutrition and contaminated blood pressure transducers. J Clin Microbiol 1987:25:1029-32.
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5. Moro ML, Maffei C, Manso E, Morace G, Polonelli L, Biavasco F. Nosocomial outbreak of systemic candidosis associated with parenteral nutrition. Infect Control Hosp Epidemiol 1990;11:27-35. 6. Burnie JP, Odds FC, Lee W, Webster C, Williams JD. Outbreak of systemic Candida albicans in intensive care unit caused by cross infection. BMJ 1985;290:746-8. 7. Burnie JP, Lee W, Williams JD, Matthews RC, Odds FC. Control of an outbreak of systemic Candida albicans. BMJ 1985;29l:1092-3. 8. Phelps M, Ayliffe GAJ, Babb JR. An outbreak of candidiasis in a special care baby unit: the use of a resistogram typing method. J Hosp Infect 1986;7:13-20. 9. Burnie JP, Matthews R, Lee W, et al. Four outbreaks of nosocomial systemic candidiasis. Epidemiol Infect 1987;99:201-11. 10. Vaudry WL, Tierney A J, Wenman WM. Investigation of a cluster of systemic Candida albicans infections in a neonatal intensive care unit. J Infect Dis 1988;158:1375-9. 11. Stevens DA, Odds FC, Scherer S. Applications of DNA typing methods to Candida albicans epidemiology and correlations with phenotype. Rev Infect Dis 1990;12:258-66. 12. Benzing GIII, Loggie J. A new retrograde method for administering drugs intravenously. Pediatrics 1973;52:420-5.
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13. Garner SS, Wiest DB. Compatibility of drugs separated by a fluid barrier in a retrograde intravenous infusion system. Am J Hosp Pharm 1990;47:604-6. 14. Reagan DR, Pfaller MA, Hollis R J, Wenzel RP. Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe. J Clin Microbiol 1990;28:2733-8. 15. Scherer S, Stevens DA. A Candida albicans dispersed, repeated gene family and its epidemiologic applications. Proc Natl Acad Sci U S A 1988;85:1452-6. 16. Weber D J, Rutala WA. Epidemiology of nosocomial fungal infections. Curt Top Med Mycol 1988;4:305-37. 17. Gelbart SM, Reinhardt GF, Greenlee HB. Multiplication of nosocomial pathogens in intravenous feeding solutions. Appl Microbiol 1973;26:874-9. 18. Goldmann DA, Martin WT, Worthington JW. Growth of bacteria and fungi in total parenteral nutrition solutions. Am J Surg 1973;126:314-8. 19. Guidelines for prevention of intravascular infections. In: Centers for Disease Control. Guidelines for the prevention and control of nosocomial infections. Atlanta: Centers for Disease Control, U.S. Department of Health and Human Services, 1981.
Clinical and laboratory observations Energy expenditure and severity of respiratory disease in very low birth weight infants receiving long-term ventilatory support C l a u d e B i l l e a u d , MD, B r u n o P i e d b o e u f , MD, a n d P h i l i p p e C h e s s e x , MD From the Perinatal Service and Research Center, H6pital Ste-Justine, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada
We attempted to determine whether the hypermetabolism of infants with branchopulmonary dysplasia was detectable during assisted ventilation. Respiratory gas e x c h a n g e variables were measured with a metabolic gas monitor in 10 infants under similar nutritional conditions. Oxygen consumption increased linearly with the need for ventilatory support (R 2 = 0.75), as documented by the ventilatory index. (J PEDIATR1992;120:461-4)
Supported by the Medical Research Council of Canada (UI-0035), and by a grant from Clintec Nutrition Canada Inc., Mississauga, Ontario, Canada. Submitted for publication June 18, 1991; accepted Oct. 11, 1991. Reprint requests: Philippe Chessex, MD, Centre de recherche, H6pital Ste-Justine, 3175 Chemin C6te Ste-Catherine, Montreal, Quebec H3T 1C5, Canada. 9/24/34283
Infants with b r o n c h o p u l m o n a r y dysplasia have elevated energy expenditure I that is often associated with poor growth. 2 W h e t h e r this growth failure is related to the increased work of b r e a t h i n g remains controversial.2, 3 These r e p o r t s of hypermetabolism were documented after several months of evolution in infants with BPD no longer requiring ventilatory support, and we believed t h a t it would be of interest to determine whether this elevated energy expendi-
Outbreaks of Candida bloodstream infection have been associated with total parenteral nutrition] -5 pressure moni-
Presented in part at the Third International Conference on Nosocomial Infections, August 1990, Atlanta, Ga., and the Society for Pediatric Research, April 199l, New Orleans, La. Submitted for publication July 25," 199l; accepted Oct. 3, 1991. Reprint requests: Robert J. Sherertz, MD, Section on Infectious Diseases, Department of Medicine, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27103. *Now at the Department of Pathology, Oregon Health Sciences University, Portland, Oregon. 9/23/34172
tors, 3,4 and intravenous additives. 1,2,s In half of the reported outbreaks the source of Candida could not be identified, 6-~~possibly because of the lack of readily available and reliable typing methods for Candida. 5, II We re-
CFU NICU TPN
Colony-forming units Neonatal intensive care unit Total parenteral nutrition
cently evaluated an outbreak of Candida bloodstream infections in a neonatal intensive care unit. Our investigation and successful intervention are summarized in this report. 455
456
Sherertz et al.
The Journal of Pediatrics March 1992
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Death
Tip
Fig. 1. Time course of Candida bloodstreaminfection in fiveinfants in NICU. Each symbolwith a Candida species label represents a blood culture positivefor that species on that day, except for those marked with arrows, which are catheter-tip cultures~ First positive blood culture was documented on Jan. 2, 1990; last was documented on Feb. 5, 1990. OUTBREAK SUMMARY In January 1990, five infants in an NICU had Candida bloodstream infections (Fig. 1). Two of the infants died of Candida infection despite therapy with amphotericin B. The five infants weighed 1400 + 700 gm (mean _+ SD), averaged 31 _+ 6 weeks of gestational age at birth, and had been hospitalized for 35 _+ 22 days at the time of Candida infection. Each infant had a patent ductus arteriosus (four of the five requiring surgical repair) and were receiving antibiotics and TPN before and during Candida infection. The attack rate for candidemia during the outbreak period (5.9%; 5/85 infants), was eight times greater than the attack rate seen in the previous year (0.7%; 4/539 infants). The outbreak began 2 months after the frequency of intravenous line changes was decreased from every 24 hour to every 72 hours. The five infants acquired candidemia in three of the four wards in the NICU. Three of the infants (patients 2, 3, and 4) had infections in one ward within 5 days of one another. The outbreak was first recognized on the day that patient 3 died (Fig. 1, day 22). At that time efforts to minimize cross infection were undertaken: (1) the use of gloves for all infant contacts was initiated, (2) chlorhexidine was selected as the standard hand-washing agent and foot-operated dispensers were installed, (3) all infected and exposed infants were placed in a single ward, and (4) the wearing of gowns was required for persons holding infants. Routine infection control practices were emphasized. All NICU and pharmacy personnel were examined for evidence of hand
dermatitis; none was found. At the same time a search was initiated for a Candida albicans reservoir (as described in the Methods section). During the next 9 days, patient 2 died and the first culture of retrograde syringe fluid grew C. albicans. The retrograde medication system (Fig. 2) was designed to allow administration through a single line of medications (such as antibiotics) that are generally incompatible with TPN fluid, to minimize the total volume given to each infant. 12, 13 As a result of the retrograde fluid culture results, a second series of interventions was carried out. On day 31, all 23 infants in the NICU had their intravenous tubing and catheters changed. The then-current practice of changing tubes every 72 hours was returned to every 24 hours. In additon, the recommendation was made that all retrograde syringes be used only once, and a nursing practice survey was initiated to determine how these syringes were actually being used. No new cases occurred after that time, and the outbreak was considered to have ended on day 35. METHODS Environmentalreservoir cultures. Three different types of solutions were cultured during the last 2 weeks of the outbreak: (1) any lotion, soap, or other such substance that could come in contact with either an infant's skin or the hands of any personnel; (2) barrier syringe solution (10% glucose) prepared by the pharmacy; (3) in-line fluids at the time that intravenous tubing was changed. Cultures were prepared by surface plating 0.1 ml of each solution onto
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Candida outbreak in a neonatal I C U
TPN Fluid
Other Fluids
Waste Syringe
Barrier Syringe
Intralipid
Flush Syringe
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457
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Fig. 2. Retrograde medication administration system. Diagram of locations where various fluid bags and syringes insert
into intravenous tubing. Distances (in inches) at bottom of figure indicate |engths of different segments of tubing. Numbers at top of figure show frequency of Candida species isolation from fluid being sampled. All isolates but one were C. albieans: the other was C. tr~piealis (barrier syringe).
Columbia blood agar plates (Carr-Scarborough Microbiologicals, Inc.. Stone Mountain. Ga.) and inoculating t ml of each solution into l0 ml of trypticase soy.broth (TSB: Becton Dickinson Microbiology Systems. Cockeysville. Md ). Plates and broths were incubated at 37 ~ C for 72 hours, and each broth was also subcultured onto a blood agar plate and incubated for an additional 72 hours. In vitro retrograde administration simulation. Retrograde medication administration was performed in our NICU by means of the components outlined in Fig. 2. The clamps below the barrier syringe and above the waste syringe were closed, isolating the waste and barrier syringes connected by 170 inches (432 cm) of tubing. Then 1 ml 10% glucose solution from the barrier syringe was injected retrogradely into the line: this was followed by injection of the medication and then an additional l ml 10% glucose solution into the same port. The syringe line segments were clamped off. the line clamps were opened, and the medication was pumped in, with the 10% glucose solution barriers above and below separating it from the TPN fluid. We simulated the retrograde administration system in our laboratory by using identical components, as diagramed in Fig. 2, except that the bags marked "'other fluids" and "Intralipid" were not present and the tubing was connected to a urine drainage bag. The TPN fluid used. which was the same as that given to the infants in the neonatal ICU. consisted of the following: 250 ml crystalline amino acid solution (Aminosyn; Abbott Laboratories), 179 m170% glucose solution (Abbott), 54 ml sterile water for injection (Ab-
bott), l0 ml multiple electrolyte concentrate (Lypholyte II; Lyphomed), 5 ml multivitamin preparation (M.V.I. Pediatric; Armour), 2 ml sodium phosphates (Lyphomed), and 1 ml trace element preparation (Pedtrace-4; Lyphomed). All components (except for the needle) were changed at either 24-, 48-, or 72-hour intervals. Retrograde administration of antibiotics was simulated by using 10% glucose as the barrier solution and phosphate-buffered saline solution in place of the antibiotic solution. Waste syringes and barrier syringes were used only once. Simulated medication was given twice in 24 hours (at 9 AM and 4 PM). Each simulated retrograde system was inoculated with C. albicans (blood culture isolate from patient 2; Fig. 1) at the start of the trial. A sterile swab dipped into phosphatebuffered saline solution containing 102 C F U / m l was used to contaminate the tip of the barrier 'syringe. Quantitative cultures from the barrier-syringe port and the flush-syringe port were obtained just before simulated medication administration. Each sample and a i:I00 dilution in phosphate-buffered saline solution were surface plated (0.1 ml) onto blood agar plates and incubated at 37 ~ C for 48 hours. Each simulated retrograde system was allowed to run for 90 hours; then material from the lumen of the 20-gauge needle was quantitatively cultured by flushing the lumen three times with 3 ml trypticase soy broth and surface plating the recovered solution as previously described. Growth curves. Three different strains of Candida isolated from patients in the NICU (two C. albicans and one Candidaparapsilosis), five gram-negative bacilli, and two Staphy-
458
Sherertz et al.
The Journal of Pediatrics March 1992
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means of an ultraviolet transilluminator and Polaroid 107C film (Polaroid Corp. Medical Products, Cambridge, Mass). Southern hydridization. Southern hybridization analysis (of C. albicans isolates only) was performed as described previously. 14The DNA probe used was 27A, a species-specific DNA probe constructed from a dispersed, repeated DNA segment from the C. albicans genome, ~5 as provided by Dr. Stewart Scherer (University of Minnesota School of Medicine, Minneapolis, Minn.). Hybridization was performed at 68 ~ C. Low-stringencY washings were performed with saline citrate at twice standard strength and 0.2% sodium dodecyl sulfate at 55 ~ C. Autoradiography was performed at - 7 0 ~ C for 30 minutes with Kodak XOMATAR film (Eastman Kodak Co., Rochester, N.Y.). Statistical analysis. All statistical comparisons of proportions had at least one expected cell size of less than 5. Therefore a two-tailed Fisher Exact Test was used for each comparison. Quantitative culture results were compared with the Mann-Whitney rank-sum test. RESULTS
. 0
24
48
Incubation --*--
Barrier Port
+
at
Room
Flush Port
72 Temp 9
96
(hr) Catheter Lumen
Fig. 3. Results of contaminating simulated retrograde medication administration system with C. albicans. Barrier port was contaminated initially, and various sites were sampled at intervals shown. A, Tubing changed every 24 hours (n = 8); B, Tubing changed every 48 hours (n = 8); C, Tubing changed every 72 hours (n = 4). Bars represent SEM. Where bars are not shown, they were smaller in size than symbol used.
Iococcus species were grown in TPN fluid, 10% glucose, and intravenous lipid emulsion (Intralipid; KabiVitrum) for 96 hours at 22 ~ C. Quantitative cultures, with dilutions and surface plating on blood agar, were prepared once or twice daily. Typing of Candida albicans strains. Ten strains of C. albicans and two strains of C. parapsilosis isolated from the patients or intravenous fluids during the outbreak investigation were sent to the Special Microbiology Laboratory at the University of Iowa (M. A. P.) for DNA typing. Each strain was identified only by a number so that the typing laboratory would be unaware of any clinical or epidemiologic associations. Restriction-endonuclease analysis o f chromosomal DNA. Stored isolates of C. albicans and C. parapsilosis were plated on Sabouraud dextrose agar and incubated at 30 ~ C for 16 hours. Chromosomal DNA was isolated and separate samples were subjected to restriction-endonuclease digestion with EcoRI and BstNI, as described previously. 14 The restriction fragments were separated by electr0Phoresis at 45 V for 16 hours on 0.7% agarose gels containing ethidium bromide. Markers for molecular weight were included in each gel. Gels were photographed by
Environmental reservoir cultures. Ninety cultures were performed on topically used solutions, including baby Soap (26 samples), hand lotion (18 samples), ointment (11 sampies), Hibiclens (Stuart Pharmaceuticals, Wilmington, Del.) hand-washing agent (10 samples), Detachal adhesive remover (Ferndale Laboratories, Inc., Ferndale, Mich. (9 samples), and miscellaneous other solutions (16 samples). All cultures of topical solutions were negative for yeasts and bacteria. No neutralization or filtration was done with antiseptic solutions; it therefore cannot be said with certainty that these solutions were not contaminated. Cultures of 38 samples of barrier solution (10% glucose) prepared by the pharmacy were negative for yeasts and bacteria. Fluid from barrier syringes and waste syringes used for retrograde medication administration (11 /267, 4.1%) were more likely to grow Candida (Fig. 2) than the other fluids sampled (1/339, 0.3%; p <0.001, Fisher Exact Test). Ten C. albicans strains were isolated from the retrograde syringe fluid, and each grew in quantities ~>50,000 C F U / m l in solution. One additional culture from a retrograde syringe grew C. parapsilosis and several syringes grew different bacteria in small numbers (<1000 CFU/ml). In vitro retrograde administration simulation. All barrier syringes were contaminated with C. albicans when sampled for culture 17 hours after inoculation (Fig. 3). Progressively higher counts of C. albicans were found in fluid aspirated through both the barrier port and the flush port at each time interval until the tubing was changed. All subsequent in-line cultures were negative for pathogens. Catheter lumina were significantly less likely to be contaminated with C. albicans if intravenous tubing was changed every 24 hours (0/8) than if it was changed every 48 hours (6/8) or every 72 hours (4/4) (p <0.006, Fisher Exact Test).
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Growth curves. Of the three different nutrient-containing fluids (10% glucose, TPN solution, and Intralipid) that were given to infants, in the NICU, only the TPN solution offered a selective growth advantage to Candida at room temperature (Fig. 4). Data on the two gram-negative organisms not shown in Fig. 4 (Acinetobacter anitratus and Enterobacter agglomerans) were essentially identical to those on the other gram-negative bacteria. Nursing survey. A survey of 43 NICU nurses identified a number of practices with the potential for facilitating line contamination and cross infection. Forty-eight percent of respondents reused syringes until empty; the syringes were stored in the refrigerator between flushes. Direct observation revealed that a syringe labeled with one infant's name occasionally was found in a different infant's line. Less frequently (16%) staff members reported that syringes with residual 10% glucose were moved from the old line to the new line when intravenous tubing was changed. Forty-nine percent of respondents stated that waste syringes were emptied after being filled and then were reinserted into the waste port; in some cases it was not clear whether waste syringes were ever discarded. Two answers were given by the nurses to explain why they were reusing the syringes. The first reason was that the nurses had been trained to perform this technique by another nurse; this practice had been going on for at least several months. The second reason was that the nurses were trying to save money by using all of the 10% glucose solution. In addition, there was a decrease in the nurse/infant staffing ratio during the outbreak period in comparison with that during the previous 12 months (3.0 vs 3.5, Nursing Productivity and Quality Software; Medicus Systems Corp., Evanston, Ill.). East Coast NICUs (level III) were surveyed regarding whether they used the retrograde method of medication administration; 7 of 12 were using the method. Candida typing. The DNA typing was carried out with 10 strains of C. albicans and two strains of C. parapsilosis isolated during the outbreak investigation (Fig. 5). All patient isolates that could be retrieved from the clinical microbiology laboratory and all isolates from our outbreak investigation were typed. All isolates of C. albicans from patients 1 (urine, lane 2), 2 (bloodstream, lane 3; retrograde syringe, lane 10), and 4 (bloodstream, lane 4; retrograde syringes, lanes 6, 7, and 9) had identical DNA-fragment profiles (type A) after digestion with EcoRI and BstNI, suggesting transmission of this strain from one patient to another. Distinctly different DNA restriction-fragment profiles were observed for a. bloodstream isolate from patient 3 (type B, lane 1), a syringe isolate from an uninfected infant (type C, lane 5), and an isolate from a 10% glucose solution from another uninfected infant (type D, lane 8). The two C. parapsilosis isolates from patient 5 had identical DNA restriction fragment profiles a n d were different from the C. albicans strains.
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Fi9. 4. Growth curves of eight different organisms in three solutions infused into infants in NICU. Each point is mean of two samples done in parallel. A, Dextrose (10%). B, Intravenous lipid emulsion (Intralipid). C, TPN fluid. Symbols: A, C. albicans (see Fig. l, patient 4, January 22); 0, C. albicans, noncase patient; II, C. parapsilosis (see Fig. 1, patient 5, January 21); A, Escherichia coli; O, Enterobacter aerogenes; [~, Klebsiella pneumoniae; V, Staphylococcus aureus; O, Staphylococcus epidermidis; solid line, Candida; dashed line, Gram-negativebacteria; dashed-dotted line, staphylococci.
Correlation of TPN and retrograde medication administration with candidemia. During the outbreak, infants receiving TPN (40/85; 47.1%) or TPN plus retrograde medications (36/40) were more likely to have candidemia than infants Who did not receive these treatments (TPN, 5/40 vs 0/45, p = 0.04; TPN plus retrograde medications, 5/36 vs 0/49, p = 0.02). Within the subgroup who received TPN, infants with candidemia had more days of TPN (20.2 + 9.7 vs 10.6 _+ 8.7 days; p = 0.03) than did those without bloodstream infection (n = 34). Infants with candidemia had more days of retrograde medication (12.2 + 4.8 vs 6.2 + 7.3 days; p = 0.02) and a greater number of line breaks because of retrograde medication administration (74.0 + 40.3 vs 24.2 + 39.4; p = 0.004) than did infants without candidemia (n = 30).
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Fig.
5. Southern hybridization autoradiography of 10 strains of C.~albicans after restriction-endonuclease digestion with EcoRI. DesignationsA, B, C, and D are distinct types based on band patterns. Origin of each strain is found in Results section.
DISCUSSION The incidence of nosocomial Candida infection, including outbreaks, has been increasing.11~ 16 The mechanisms for many outbreaks have not been identified.6-t~ The Candida outbreaks with identified mechanisms of transmission, including one NICU outbreak, 3 were caused by extrinsic contamination of intravenously administered medications or vascular-access apparatus. 15 The mechanism for the outbreak that we investigated falls into the latter category. In our NICU five infants apparently acquired Candida bloodstream infection as a result of contaminated retrograde medication syringes. Candida bloodstream infection Occurred only in infants receiving retrograde medications in association With TPN. Infants in the retrograde medication subgroup wh o acquired Candida bloodstream infection had the greatest number of line breaks into the retrograde system and therefore the greatest risk of line contamination. Retrograde medication syringes were more likely to be contaminated by Candida than were other fluid reservoirs attached to the intravenous tubing during the outbreak period. Finally, molecular typing demonstrated for two of the infants that the same strain of C. albicans was isolated botfi from the retrograde syringes and from the bloodstream. The Candida strains causing the outbreak were both clustered and multifocal in origin. The multifocal origin of the outbreak suggests a generalized predisposition toward infection by the genus Candida. Our in vitro growth curves
The Journal of Pediatrics March 1992
demonstrated that Candida species have a selective growth advantage in TPN fluid administered to the infants in our NICU but do not have this advantage with the Intralipid or 10% glucose solutions. One previous study suggested that protein hydrolysate solutions by themselves are selective for Candida rather than bacteria, whereas synthetic amino acid solutions are not) 7 A second study found that casein hydrolysate plus dextrose was not selective for Candida but that a synthetic amino acid solution plus dextrose was selective.tS Our TPN solution contained synthetic amino acids plus dextrose in addition to other additives; the contribution of the other additives to the selective growth of Candida is unknown. Although the retrograde syringes were initially contaminated, it was the TPN fluid that probably allowed selective replication of yeasts. The precipitating event for this outbreak may have been the reduction in the frequency with which intravenous tubing was changed, from every 24 hours to every 72 hours, in line with hospital policy. Current Centers for Disease Control recommendations state that it is safe to change intravenous tubing every 48 hours.r9 Although our outbreak was associated with suboptimal nursing practice that was possibly accentuated by a decrease in the nurse/infant ratio, our in vitro simulation suggests that the Centers for Disease Control recommendations may not be optimal for clinical settings where lines containing TPN solution must be opened repeatedly to administer therapy. The safest approach to the administration of TPN and incompatible intravenous medications to infants in the N I C U remains to be determined. With proper technique it may be feasible to safely change intravenous tubing in the retrograde system less frequently than every 24 hours: however, until data support this contention, it seems prudent to change intravenous tubing every 24 hours. Because of the high risk for contamination of the retrograde system by Candida and the finding that more than 50% of 12 East Coast level III NICUs used this method of medication administration, other NICUs should carefully examine their TPN administration practices to ensure safety. We greatly appreciate the technical skills of Richard Hollis. REFERENCES
1. Plouffe JF, Brown DG. Silva J Jr. Eck T. Stricof RL. Fekety R Jr. Nosocomialoutbreak of Candida parapsilosis fungemia related to intravenous infusions. Arch Intern Med 1977: 137:1686-9. 2. Solomon SL. Khabbaz RF. Parker RH. et al. An outbreak of Candida parapsilosis bloodstream infections in patients receiving parenteral nutrition. J Infect Dis 1984:149:98-102. 3. Solomon SL, Alexander H, Eley JW, et al. Nosocomial fungemaa in neonates associatedwith intravascular pressuremonitoring devices. Pediatr Infect Dis 1986:5:680-5. 4. Weems JJ JR, Chamberland ME, Ward J. Willy M, Padhye AA. Solomon SL. Candida parapsilosis fungemla associated with parenteral nutrition and contaminated blood pressure transducers. J Clin Microbiol 1987:25:1029-32.
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5. Moro ML, Maffei C, Manso E, Morace G, Polonelli L, Biavasco F. Nosocomial outbreak of systemic candidosis associated with parenteral nutrition. Infect Control Hosp Epidemiol 1990;11:27-35. 6. Burnie JP, Odds FC, Lee W, Webster C, Williams JD. Outbreak of systemic Candida albicans in intensive care unit caused by cross infection. BMJ 1985;290:746-8. 7. Burnie JP, Lee W, Williams JD, Matthews RC, Odds FC. Control of an outbreak of systemic Candida albicans. BMJ 1985;29l:1092-3. 8. Phelps M, Ayliffe GAJ, Babb JR. An outbreak of candidiasis in a special care baby unit: the use of a resistogram typing method. J Hosp Infect 1986;7:13-20. 9. Burnie JP, Matthews R, Lee W, et al. Four outbreaks of nosocomial systemic candidiasis. Epidemiol Infect 1987;99:201-11. 10. Vaudry WL, Tierney A J, Wenman WM. Investigation of a cluster of systemic Candida albicans infections in a neonatal intensive care unit. J Infect Dis 1988;158:1375-9. 11. Stevens DA, Odds FC, Scherer S. Applications of DNA typing methods to Candida albicans epidemiology and correlations with phenotype. Rev Infect Dis 1990;12:258-66. 12. Benzing GIII, Loggie J. A new retrograde method for administering drugs intravenously. Pediatrics 1973;52:420-5.
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13. Garner SS, Wiest DB. Compatibility of drugs separated by a fluid barrier in a retrograde intravenous infusion system. Am J Hosp Pharm 1990;47:604-6. 14. Reagan DR, Pfaller MA, Hollis R J, Wenzel RP. Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe. J Clin Microbiol 1990;28:2733-8. 15. Scherer S, Stevens DA. A Candida albicans dispersed, repeated gene family and its epidemiologic applications. Proc Natl Acad Sci U S A 1988;85:1452-6. 16. Weber D J, Rutala WA. Epidemiology of nosocomial fungal infections. Curt Top Med Mycol 1988;4:305-37. 17. Gelbart SM, Reinhardt GF, Greenlee HB. Multiplication of nosocomial pathogens in intravenous feeding solutions. Appl Microbiol 1973;26:874-9. 18. Goldmann DA, Martin WT, Worthington JW. Growth of bacteria and fungi in total parenteral nutrition solutions. Am J Surg 1973;126:314-8. 19. Guidelines for prevention of intravascular infections. In: Centers for Disease Control. Guidelines for the prevention and control of nosocomial infections. Atlanta: Centers for Disease Control, U.S. Department of Health and Human Services, 1981.
Clinical and laboratory observations Energy expenditure and severity of respiratory disease in very low birth weight infants receiving long-term ventilatory support C l a u d e B i l l e a u d , MD, B r u n o P i e d b o e u f , MD, a n d P h i l i p p e C h e s s e x , MD From the Perinatal Service and Research Center, H6pital Ste-Justine, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada
We attempted to determine whether the hypermetabolism of infants with branchopulmonary dysplasia was detectable during assisted ventilation. Respiratory gas e x c h a n g e variables were measured with a metabolic gas monitor in 10 infants under similar nutritional conditions. Oxygen consumption increased linearly with the need for ventilatory support (R 2 = 0.75), as documented by the ventilatory index. (J PEDIATR1992;120:461-4)
Supported by the Medical Research Council of Canada (UI-0035), and by a grant from Clintec Nutrition Canada Inc., Mississauga, Ontario, Canada. Submitted for publication June 18, 1991; accepted Oct. 11, 1991. Reprint requests: Philippe Chessex, MD, Centre de recherche, H6pital Ste-Justine, 3175 Chemin C6te Ste-Catherine, Montreal, Quebec H3T 1C5, Canada. 9/24/34283
Infants with b r o n c h o p u l m o n a r y dysplasia have elevated energy expenditure I that is often associated with poor growth. 2 W h e t h e r this growth failure is related to the increased work of b r e a t h i n g remains controversial.2, 3 These r e p o r t s of hypermetabolism were documented after several months of evolution in infants with BPD no longer requiring ventilatory support, and we believed t h a t it would be of interest to determine whether this elevated energy expendi-