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Improving Survival of Vulnerable Infants Increases Neonatal Intensive Care Unit Nosocomial Infection Rate
Nagma Zafar, MD;
Colleen M. Wallace, MD;
Patricia Kieffer, RN;
Patricia Schroeder, RN;
Mario Schootman, PhD;
Aaron Hamvas, MD
Arch Pediatr Adolesc Med. 2001;155:1098-1104.
ABSTRACT
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Objective To determine the factors associated with an increasing rate of nosocomial
infections in infants with very low birth weights.
Methods Retrospective review of clinical and nosocomial infection databases
for all infants with birth weights of 1500 g or less admitted to an academic
neonatal intensive care unit between January 1, 1991, and December 31, 1997
(N = 1184). Two study periods were compared: 1991-1995 and 1996-1997.
Results Among the 1085 infants who survived beyond 48 hours, the proportion
who developed nosocomial infections increased from 22% to 31% (P = .001) and the infection rate increased from 0.5 to 0.8 per 100
patient-days (P<.001) during the period from 1996
to 1997. In that same period, the median duration of indwelling vascular access
increased from 10 to 16 days (P<.001), and the
median duration of mechanical ventilation increased from 7 to 12 days (P<.001). Although the device-specific rate of bloodstream
or respiratory infections did not change, the increase in infections was directly
attributable to the increasing proportion of infants who required these devices.
In both study periods, the peak incidence of initial infection occurred between
10 and 20 days of age. For the entire sample, proportional hazard models identified
birth weight, duration of vascular access, and postnatal corticosteroid exposure
as significant contributors to the risk of infection.
Conclusions The increasing number of technology-dependent infants was the primary
determinant in the increase of nosocomial infections. Because these infections
occur in a small proportion of infants, understanding the host factors that
contribute to this vulnerability is necessary to decrease nosocomial infections
in neonatal intensive care units.
INTRODUCTION
IMPROVEMENTS in obstetrical and neonatal intensive care have reduced
the morbidity and mortality rates of infants with very low birth weights.
Antibiotic administration at the onset of preterm labor or rupture of maternal
amniotic membranes decreases the risk of intrapartum acquisition of pathogens
and may prolong pregnancy. Antenatal corticosteroid administration and postnatal
surfactant administration decrease the incidence, severity, and mortality
of neonatal respiratory distress syndrome and may decrease the likelihood
of bacteremia in these infants.1, 2, 3, 4, 5, 6, 7, 8
Although these interventions effectively improve pulmonary outcomes, nosocomially
acquired infections still affect up to 25% of infants in neonatal intensive
care units (NICUs), with a disproportionate share occurring in infants with
a birth weight of less than 1500 g.9, 10, 11, 12, 13, 14
Infection control practices and surveillance are invaluable for preventing
acquisition and spread of these infections and for identifying environmental
factors that may contribute to clusters of infections. However, extensive
investigations often fail to yield specific sources, and the clusters may
spontaneously disappear. This suggests that environmental or host factors
that have yet to be identified also contribute to the acquisition of nosocomial
infections.
During ongoing routine surveillance, we noted an increase in the nosocomial
infection rate in the St Louis Children's Hospital NICU (St Louis, Mo) and
were concerned that changes in the environment or care practices might be
contributing to this higher infection rate. We were further concerned, based
on the identification of clusters of colonization with gram-negative organisms,
that the microbiological spectrum of the nosocomial infections occurring in
our NICU was changing. Therefore, to determine if the rate and microbiological
spectrum of nosocomial infections were changing and to further determine if
peripartum antibiotic usage might be contributing to a change in epidemiology,
we reviewed all nosocomial infections in infants with birth weights of 1500
g or less in the NICU from 1991 to 1997.
SUBJECTS AND METHODS
We retrospectively reviewed the clinical and nosocomial infection databases
for all infants admitted between January 1, 1991, and December 31, 1997 (N
= 4827). Because the overall infection rate increased in 1996, we divided
the data into 2 study periods: 1991-1995 and 1996-1997 (Figure 1). Although infants with very low birth weights ( 1500
g) made up 25% of NICU admissions during the 7 years studied, they accounted
for 92% of nosocomial infections in the NICU. Therefore, we limited the study
to this group (N = 1184).
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Figure 1. Annual nosocomial infection rate
per 1000 patient-days for all infants in the St Louis Children's Hospital
neonatal intensive care unit (St Louis, Mo) for the 1991-1997 period. The
numbers above the bars indicate the total number of patient-days in the year.
After a decrease between 1991 and 1992, the rate increased steadily but not
significantly until 1996.
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Because we were interested only in nosocomially acquired infections,
we excluded infections identified within 48 hours of admission and transplacentally
acquired infections. Definitions for nosocomial infections were in accordance
with those of the National Nosocomial Infections Surveillance (NNIS) System
of the Centers for Disease Control and Prevention.15
Infections, regardless of source, were included only if a positive bacterial
or fungal culture occurred in association with a clinical syndrome and initiation
of antibiotic therapy. We also excluded 16 positive eye drainage cultures
and 11 positive wound cultures. The surveillance period for each infant ended
at death, discharge, transfer to another facility, or the end of the study
period. Information collected included birth weight, gestational age, length
of stay in the NICU, survival, number and source of infections, age at the
time of infection, the organism(s) responsible, exposure to corticosteroids
while in the NICU, and presence and duration of mechanical ventilation or
long-term vascular access. The duration of long-term vascular access was calculated
as the total number of days during which an umbilical venous or arterial catheter,
Broviac catheter, peripherally inserted central venous catheter, or peripheral
arterial catheter was present.
To determine if maternal antibiotic or corticosteroid administration
contributed to the risk of acquiring a nosocomial infection, we obtained computerized
pharmacy records (available from July 1993 forward) for every mother who gave
birth at our primary obstetrical service to an infant with a very low birth
weight who was transferred to the NICU (n = 338).
The data were analyzed using Statistical Analysis System software (SAS
Institute, Cary, NC). t Tests were used to compare
normally distributed continuous variables; Wilcoxon rank sum comparisons were
used for nonparametric data. Comparisons of categorical data and estimates
of relative risk (RR) between groups were performed with Cochran-Mantel-Haenszel  2 analyses, and 2-tailed P values were calculated.
We also developed proportional hazard models to identify independent factors
that contributed to the risk of infection or death in a multivariate model.16, 17 The Washington University Human Studies
Committee approved the study.
RESULTS
DEMOGRAPHICS
Of the 1184 infants with very low birth weights admitted to the NICU
during the study period, 99 had lengths of stay less than 48 hours and thus
were excluded. Of these 99 infants, 84 died within 48 hours of birth; the
remaining 15 were briefly admitted after their neonatal period for specialized
procedures. Of the 84 infants who died, 66 were born in the 1991-1995 period,
and 18 were born in the 1996-1997 period (8% and 5% of the study population,
respectively; P = .06). These infants had median
birth weights of 727 g and 631 g between 1991 and 1995, and 1996 and 1997,
respectively (P = .06), and median gestational ages
of 25 and 24 weeks, respectively (P = .08).
After this exclusion, the final study population contained 1085 infants,
with 747 and 338 infants in the 1991-1995 and 1996-1997 groups, respectively.
There were no differences between the 1991-1995 and 1996-1997 periods with
respect to birth weight distribution, race, sex, survival after 48 hours,
or length of stay (Table 1). Gestational
age was statistically but not clinically different between the 2 study periods:
28.2 vs 27.8 weeks, 1991-1995 and 1996-1997, respectively. Postnatal corticosteroid
use increased significantly in the later study period. Also in this period,
survival through the first 48 hours of life increased from 92% to 95% (P = .06) (Table 1).
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Table 1. Demographic Data of Infants With Very Low Birth Weights Admitted
to the Neonatal Intensive Care Unit*
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INFECTION RATE
The proportion of infants who experienced at least 1 infection increased
from 22% to 31% in the later surveillance period (P
= .001) (Table 2). The number
of infections normalized for patient-days was also significantly higher in
the 1996-1997 period. Overall, 266 infants acquired 391 infections; 30% of
the study group accounted for 52% of the infections, with a similar proportion
in each study period. The peak incidence of initial infection in both study
periods occurred between 10 and 20 days of age, with 73% of all initial infections
arising in this interval (Figure 2). Forty-three infants (6%) in the 1991-1995 period and 31 infants (9%) in the
1996-1997 period experienced more than 1 infection (P
= .04). In both periods, approximately 55% of the subsequent infections occurred
by 60 days of age.
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Table 2. Birth Weight–Specific Rates of Infection*
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Figure 2. The incidence of initial infection
in infants with very low birth weights according to age in specified intervals.
The incidence was calculated by dividing the number of infants who developed
their first infection within the interval by the difference between the number
of infants hospitalized at the beginning of the interval and those with previous
infections who were still hospitalized. The peak incidence occurred in the
10- to 20-day interval for both the 1991-1995 and 1996-1997 study periods.
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DEVICE USE AND INFECTION
The proportion of infants with long-term vascular catheters was significantly
greater in the later study period (88% vs 94% of infants, 1991-1995 and 1996-1997,
respectively; P = .002). In addition, the median
duration of catheter use increased in the later study period from 10 days
per infant to 16 days per infant (range, 0-193 days; P<.001),
and from 30 to 42 catheter-days per 100 patient-days (P<.001). Despite the increase in use of vascular catheters, the rate
of bacteremia normalized for duration of vascular access did not change (Figure 3A and B). Similarly, the proportion
of infants who required mechanical ventilation increased in the later study
period (90% vs 97%; P = .001). The median duration
of ventilation increased from 7 days per infant (range, 0-200 days) to 12
days per infant (range, 0-206 days; P<.001) and
from 29 to 38 ventilator-days per 100 patient-days (P<.001).
However, the rate of respiratory infections normalized for ventilator days
did not change (Figure 4A and B).
These device use and associated infection rates were comparable with those
published by the NNIS for the period from 1990 to 1998 (data not shown).15 The overall increase in infections was directly attributable
to the increased number of infants who required these devices and their duration
of use in the later period.
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Figure 3. Vascular catheter use and bacteremia
by birth weight group. A, The number of catheter-days was significantly greater
in the 1996-1997 period for all birth weight subgroups (P<.001 for all). B, The number of episodes of bacteremia normalized
for vascular catheter-days was not different for any of the birth weight subgroups
between the 2 periods (P>.20 for all).
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Figure 4. Ventilator use and respiratory
infections by birth weight group. A, The number of ventilator-days was significantly
greater in the 1996-1997 period for all birth weight subgroups (P<.001 for all). B, The number of respiratory infections normalized
for ventilator-days was not different for any of the birth weight subgroups
between the 2 periods (P>.30 for all).
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SOURCE AND SPECTRUM OF ORGANISMS
We found that 53% of the organisms were isolated from the bloodstream,
27% from the respiratory tract, 14% from the urinary tract, 4% from the gastrointestinal
tract, and 1% from the cerebrospinal fluid. This distribution was similar
in the 2 study periods. To determine if the increasing number of infections
was accompanied by a shift in the spectrum of organisms, we analyzed the annual
distribution of the specific pathogens (Table 3). Some annual variation in the types of organisms reflected
small clusters of infection. The relative proportion of gram-negative to gram-positive
organisms was not significantly greater in the 1996-1997 period (0.8 and 1.0,
1991-1995 and 1996-1997, respectively; P = .17);
this was also true for fungal infections.
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Table 3. Annual Distribution of Specific Organisms*
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RISK OF INFECTION
To determine the degree to which different factors might have influenced
the increased rate of infection, we developed a proportional hazard model
for the entire sample to evaluate the risk of nosocomial infection (treated
as a dichotomous variable) with respect to birth weight (treated as a continuous
variable), study period, exposure to corticosteroids while in the NICU, and
duration of mechanical ventilation and long-term vascular access (treated
as continuous variables). After controlling for these factors, lower birth
weight (RR, 1.002 per gram; 95% confidence interval [CI], 1.001-1.002), corticosteroid
exposure (RR, 1.7; 95% CI, 1.2-2.3), and duration of central vascular access
(RR, 1.01 per day; 95% CI, 1.005-1.015) significantly influenced the risk
of infection. The duration of mechanical ventilation did not significantly
influence the risk of infection (RR, 1.005 per day; 95% CI, 0.999-1.010).
To determine if maternal antibiotic or corticosteroid administration
contributed to the risk of nosocomial infection, we evaluated the subset of
infants born at our primary obstetrical service. This subset was comparable
with the remainder of the population with respect to birth weight, gestational
age, infection rate, and device use (data not shown). We then developed another
proportional hazard model in which we added maternal antibiotic and corticosteroid
administration (treated as dichotomous variables) to birth weight and duration
of device use (treated as continuous variables) to evaluate the risk of nosocomial
infection. In this model, only lower birth weight (RR, 1.003 per gram; 95%
CI, 1.002-1.004) and duration of central vascular access (RR, 1.008 per day;
95% CI, 1.001-1.015) significantly contributed to the risk of infection. In
separate models using this subset of infants, none of these parameters significantly
influenced the occurrence of nosocomial infections caused by yeast, gram-negative,
or gram-positive organisms, most likely because of inadequate power in the
analysis.
RISK OF DEATH
Deaths directly due to infection increased from 2% to 4% of the study
population in the later period (P = .02). In addition,
in each study period, the risk of death was significantly greater for infants
who experienced an infection (RR, 1.8; 95% CI, 1.3-2.5 and RR, 1.8; 95% CI,
1.3-2.7 in the earlier and later period, respectively). Despite the greater
number of infections in the later period, the attributable risk of mortality
(9% and 13%, respectively) did not change (P = .09).
In a proportional hazard model using the entire sample in which the risk of
death was evaluated with respect to infection during hospitalization, study
period, birth weight, corticosteroid exposure, and duration of device use,
only lower birth weight (RR, 1.005 per gram; 95% CI, 1.004-1.006) and corticosteroid
exposure (RR, 0.4; 95% CI, 0.2-0.7) significantly influenced the risk of death.
Duration of central vascular access or mechanical ventilation was of borderline
significance (RR, 0.99 per day; 95% CI, 0.98-1.0 for both variables). In separate
proportional hazard models in which the risk of death was analyzed with respect
to the source of infection (treated as categorical variables: bloodstream,
respiratory tract, etc) or the type of organism (treated as categorical variables:
gram-negative, gram-positive, or yeast), along with birth weight and device
use, neither the source of infection nor the type of organism influenced the
risk of death.
COMMENT
We observed a significant increase in the rate of nosocomially acquired
infections for infants with very low birth weights in the St Louis Children's
Hospital NICU between 1991 and 1997. We also found an increase in the frequency
and duration of device use that paralleled the increase in infection rate,
which suggests a larger population of technology-dependent infants who were
vulnerable to acquiring infections. Although we did not have indexes to quantify
the severity of illness, the observation that the duration of central catheter
use or mechanical ventilation increased in the 1996-1997 period suggests a
sicker population and does not simply reflect an increase in the perceived
need for these interventions. Despite the greater use of these devices, infection
rates associated with them did not change significantly over time, which suggests
that practices relating to ventilator and indwelling vascular catheter management
did not contribute to changes in the overall infection rate. This lack of
change in device-associated infections occurred in the presence of 2 significant
practice modifications: a decrease in the frequency with which ventilator
tubing was changed (from every 3 days to every 2 weeks) and the development
of a nursing team dedicated to placement of percutaneous central venous catheters.
Despite these practice changes, our cumulative rates of device-associated
infection were comparable with those reported by the NNIS between 1990 and
1998.15 We also found that the 2 most prevalent
sites of infection, the bloodstream and the respiratory tract, were similar
in distribution to other reported studies.18
We were surprised to find a similar microbiological spectrum between
the early and later periods of the study, specifically yeast and gram-negative
infections, a spectrum that was also comparable with other published reports.9, 18, 19, 20 Although
periodic clusters of organisms suggested a component of horizontal transmission
and created the impression that an individual organism's prevalence was increasing,
these clusters resolved without explanation or apparent trend. However, the
observation that the proportion of infections caused by gram-negative organisms
appeared to increase in the later study period suggests a trend that bears
monitoring. Throughout the entire study period, ampicillin sodium and gentamicin
sulfate were used almost exclusively for presumptive treatment of intrapartum-acquired
pathogens in the 48 hours after delivery; vancomycin hydrochloride and gentamicin
were used after 7 days.
Antibiotic or corticosteroid administration, either in the peripartum
or neonatal period, may alter the microbiological spectrum of organisms or
increase the risk of infection, especially in the first days after birth.21, 22, 23 However, these interventions
may also influence the spectrum of later-onset infections thought to be nosocomially
acquired, an issue that has not been previously evaluated. We did not have
the opportunity to examine the antimicrobial sensitivity patterns of the organisms,
nor did we examine the rate or microbiological spectrum of neonatal early-onset
infections, either of which may be influenced by intrapartum antibiotic administration.21, 22 Although we did not have data on
maternal antibiotic or corticosteroid administration for the entire population
or duration of the study, these agents did not appear to significantly influence
the risk or microbiologic distribution of nosocomial infections in the subset
of infants for whom data were available.
Postnatal dexamethasone sodium phosphate administration to treat bronchopulmonary
dysplasia has not been reported to increase the risk of infection. However,
after controlling for study period and other clinical factors, we found that
postnatal corticosteroid use contributed to a higher risk of infection yet
a lower risk of death.24, 25, 26
Because our data did not permit analysis of the temporal relationship between
postnatal corticosteroid administration and infection, we could not assess
the attributable risk of infection due to corticosteroid use. A larger prospective
analysis would be more appropriate to address the effects of peripartum interventions
and to test hypotheses about other practices that may influence long-term
risk of infection.
Current epidemiologic techniques designed to identify risk factors for
nosocomial infection in NICUs have consistently yielded similar results: the
infants at greatest risk of nosocomial infection are the smallest and require
the most interventions, and infection is a risk factor for adverse outcome.12, 13, 20, 27 Two
other observations in our study warrant discussion. First, a small population
of infants contributed disproportionately to the infection rate, and second,
73% of nosocomial infections occurred between 10 and 20 days of age, which
is consistent with a median onset of 15 to 17 days in other reports of nosocomial
bloodstream infections.12, 19, 28, 29
These observations suggest that a subset of infants with very low birth weights
may have an underlying genetic or immunologic susceptibility to the pathogenic
effect of ubiquitous organisms at critical periods in their postnatal development.
For instance, in infants with evolving lung injury, disruption of innate immunologic
factors such as surfactant proteins A or D or granulocyte-macrophage colony-stimulating
factor could permit organisms to establish more widespread infection.30, 31, 32, 33, 34
Along with attempts to decrease device-associated infection rates and to provide
meticulous environmental surveillance and education about infection control
procedures, efforts to understand and modify these biologic vulnerability
factors will be necessary to significantly decrease the nosocomial infection
rate in NICUs.
AUTHOR INFORMATION
Accepted for publication March 27, 2001.
The authors would like to thank Gregory Storch, MD, for thoughtful suggestions
for data analysis and careful review of the manuscript, and Laura Noce, RN,
BSN, for providing nosocomial infection data.
What This Study Adds
Newborns with low birth weights who require intensive care are at increased
risk for nosocomial infection, primarily because of the need for invasive
technology. Despite rigorous infection control measures, we noticed an increased
rate of nosocomial infection in the St Louis Children's Hospital NICU.
The increasing proportion of technology-dependent infants in our NICU
was the predominant factor contributing to the increasing infection rate.
The peak incidence for nosocomial infections occurred between 10 and 20 days
of age, and the second-highest incidence occurred between 3 and 10 days of
age. This observation suggests that biological factors in the infant and/or
mother, rather than environmental factors, may contribute to the risk of infection.
These factors need to be identified and examined in more detail.
From the Edward Mallinckrodt Department of Pediatrics (Drs Zafar, Wallace,
and Hamvas and Mss Kieffer and Schroeder), Washington University School of
Medicine and St Louis Children's Hospital; and the Department of Internal
Medicine (Dr Schootman), Washington University School of Medicine, St Louis,
Mo.
Corresponding author: Aaron Hamvas, MD, Division of Newborn Medicine,
St Louis Children's Hospital, One Children's Place, St Louis, MO 63110 (e-mail: hamvas{at}kids.wustl.edu).
REFERENCES
| |
1. Mercer BM, Miodovnik M, Thurnau GR, et al for the National Institute of Child Health and Human Development Maternal-Fetal
Medicine Units Network. Antibiotic therapy for reduction of infant morbidity after preterm
premature rupture of the membranes: a randomized controlled trial. JAMA. 1997;278:989-995.
FREE FULL TEXT
2. King J, Flenady V. Antibiotics for preterm labour with intact membranes. Cochrane Database Syst Rev. 2000;2:CD000246.
3. Kenyon S, Boulvain M. Antibiotics for preterm premature rupture of membranes. Cochrane Database Syst Rev. 2000;2:CD001058.
4. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev. 2000;2:CD000065.
5. Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. Bethesda, Md: National Institutes of Health; 1994:1-24. NIH consensus
statement, vol 12, No. 2.
6. Jobe AH. Pulmonary surfactant therapy. N Engl J Med. 1993;328:861-868.
FREE FULL TEXT
7. Soll RF. Synthetic surfactant for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev. 2000;2:CD001149.
8. Soll RF. Natural surfactant extract versus synthetic surfactant for neonatal
respiratory distress syndrome. Cochrane Database Syst Rev. 2000;2:CD000144.
9. Hemming VG, Overall JC, Britt MR. Nosocomial infections in a newborn intensive care unit: results of
forty-one months of surveillance. N Engl J Med. 1976;294:1310-1316.
ABSTRACT
10. Maguire GC, Nordin J, Myers MG, Koontz FP, Hierholzer W, Nassif E. Infections acquired by young infants. AJDC. 1981;135:693-698.
11. Gaynes RP, Martone WJ, Culver DH, et al. Comparison of rates of nosocomial infections in neonatal intensive
care units in the United States: National Nosocomial Infections Surveillance
System. Am J Med. 1991;91:192S-196S.
12. Khadilkar V, Tudehope D, Fraser S. A prospective study of nosocomial infection in a neonatal intensive
care unit. J Paediatr Child Health. 1995;31:387-391.
ISI
| PUBMED
13. Moro ML, De Toni A, Stolfi I, Carrieri MP, Braga M, Zunin C. Risk factors for nosocomial sepsis in newborn intensive and intermediate
care units. Eur J Pediatr. 1996;155:315-322.
ISI
| PUBMED
14. Baltimore RS. Neonatal nosocomial infections. Semin Perinatol. 1998;22:25-32.
FULL TEXT
|
ISI
| PUBMED
15. National Nosocomial Infections Surveillance (NNIS) System report: data
summary from October 1986-April 1998: issued June 1998. Am J Infect Control. 1998;26:522-533.
FULL TEXT
|
ISI
| PUBMED
16. Rosner B. Fundamentals of Biostatistics. 2nd ed. Boston, Mass: Duxbury Press; 1986.
17. Mausner JS, Bahn AK. Epidemiology. Philadelphia, Pa: WB Saunders Co; 1974.
18. Gaynes RP, Edwards JR, Jarvis WR, Culver DH, Tolson JS, Martone WJ. Nosocomial infections among neonates in high-risk nurseries in the
United States: National Nosocomial Infections Surveillance System. Pediatrics. 1996;98:357-361.
FREE FULL TEXT
19. Sanghvi KP, Tudehope DI. Neonatal bacterial sepsis in a neonatal intensive care unit: a 5 year
analysis. J Paediatr Child Health. 1996;32:333-338.
ISI
| PUBMED
20. Isaacs D, Barfield C, Clothier T, et al. Late-onset infections of infants in neonatal units. J Paediatr Child Health. 1996;32:158-161.
ISI
| PUBMED
21. Towers CV, Carr MH, Padilla G, Asrat T. Potential consequences of widespread antepartal use of ampicillin. Am J Obstet Gynecol. 1998;179:879-883.
FULL TEXT
|
ISI
| PUBMED
22. Joseph TA, Pyati SP, Jacobs N. Neonatal early-onset Escherichia coli disease:
the effect of intrapartum ampicillin. Arch Pediatr Adolesc Med. 1998;152:35-40.
FREE FULL TEXT
23. Wright LL, Verter J, Younes N, et al. Antenatal corticosteroid administration and neonatal outcome in very
low birth weight infants: the NICHD Neonatal Research Network. Am J Obstet Gynecol. 1995;173:269-274.
FULL TEXT
|
ISI
| PUBMED
24. Arias-Camison JM, Lau J, Cole CH, Frantz III ID. Meta-analysis of dexamethasone therapy started in the first 15 days
of life for prevention of chronic lung disease in premature infants. Pediatr Pulmonol. 1999;28:167-174.
FULL TEXT
|
ISI
| PUBMED
25. Halliday HL, Ehrenkranz RA. Moderately early (7-14 days) postnatal corticosteroids for preventing
chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2000;2:CD001144.
26. Halliday HL, Ehrenkranz RA. Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease
in preterm infants. Cochrane Database Syst Rev. 2000;2:CD001145.
27. Mullett MD, Cook EF, Gallagher R. Nosocomial sepsis in the neonatal intensive care unit. J Perinatol. 1998;18:112-115.
PUBMED
28. Brodie SB, Sands KE, Gray JE, et al. Occurrence of nosocomial bloodstream infections in six neonatal intensive
care units. Pediatr Infect Dis J. 2000;19:56-65.
FULL TEXT
|
ISI
| PUBMED
29. Fanaroff AA, Korones SB, Wright LL, et al. Incidence, presenting features, risk factors and significance of late
onset septicemia in very low birth weight infants: the National Institute
of Child Health and Human Development Neonatal Research Network. Pediatr Infect Dis J. 1998;17:593-598.
FULL TEXT
|
ISI
| PUBMED
30. Awasthi S, Coalson JJ, Crouch E, Yang F, King RJ. Surfactant proteins A and D in premature baboons with chronic lung
injury (bronchopulmonary dysplasia): evidence for an inhibition of secretion. Am J Respir Crit Care Med. 1999;160:942-949.
FREE FULL TEXT
31. LeVine AM, Kurak KE, Bruno MD, Stark JM, Whitsett JA, Korfhagen TR. Surfactant protein-A–deficient mice are susceptible to Pseudomonas aeruginosa infection. Am J Respir Cell Mol Biol. 1998;19:700-708.
FREE FULL TEXT
32. LeVine AM, Bruno MD, Huelsman KM, Ross GF, Whitsett JA, Korfhagen TR. Surfactant protein A–deficient mice are susceptible to group
B streptococcal infection. J Immunol. 1997;158:4336-4340.
ABSTRACT
33. Vaandrager AB, van Golde LM. Lung surfactant proteins A and D in innate immune defense. Biol Neonate. 2000;77(suppl 1):9-13.
34. LeVine AM, Reed JA, Kurak KE, Cianciolo E, Whitsett JA. GM-CSF–deficient mice are susceptible to pulmonary group B streptococcal
infection. J Clin Invest. 1999;103:563-569.
ISI
| PUBMED
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