Journal of Infection (2007) 54, 212e220

www.elsevierhealth.com/journals/jinf

REVIEW

Nosocomial infections in paediatric and neonatal intensive care units

Urrea Ayala Mireya a,*, Pons Odena Mart b, Krauel Vidal Xavier c, d n Latorre Otin Cristina , Mart Mateo Miguel e, Campins Mart Magda f
u, u, Hospital Infections Program, Hospital Sant Joan de De Pg. Sant Joan de De 2, 08950 Esplugues, Barcelona, Spain b u, u, Paediatric Intensive Care Unit, Hospital Sant Joan de De Pg. Sant Joan de De 2, 08950 Esplugues, Barcelona, Spain c u, u, Neonatal Care Unit, Hospital Sant Joan de De Pg. Sant Joan de De 2, 08950 Esplugues, Barcelona, Spain d u, u, Microbiology Service, Hospital Sant Joan de De Pg. Sant Joan de De 2, 08950 Esplugues, Barcelona, Spain e n, `noma de Barcelona, Barcelona, Spain Biostatistics Unit, Hospital Vall dHebro Universitat Auto f n, Department of Preventive Medicine and Epidemiology, Hospital Vall dHebro `noma de Barcelona, Barcelona, Spain Universitat Auto
Accepted 18 March 2006 Available online 6 May 2006
a

KEYWORDS
Nosocomial infection; Paediatric patients; Incidence

Summary Objective: To describe the epidemiological prole of NI in the PICU and NICU, and its related risk factors. Design: A prospective surveillance study from May through October 2000 was performed in the PICU and NICU in a tertiary care university hospital in Barcelona. Results: During the study period, 257 patients were admitted to the PICU and 121 to the NICU. The incidence rate of NI was 26.5 infections per 100 admissions and 1.7 infections per 100 patient-days in the PICU. In the NICU, the incidence rate of NI was 74.3 infections per 100 admissions and 2.7 infections per 100 patient-days. Bacteraemia was the most frequent episode of NI in both units. The most common microorganisms isolated were Gram-positive bacteria (47.2% and 72.7%) in each unit. The factors more frequently associated with NI in the PICU were as follows: patient age under 1 year (RR 5.0; 95% CI 1.6e15.4), class IV of CCS (RR 3.7; 95% CI 1.2e11.1), and mechanical ventilation (RR 2.5; 95% CI 1.0e6.0). In the NICU, the most signicant predisposing factors were birth weight less than 1000 g (RR 2.8; 95% CI 1.0e8.0), umbilical arterial catheterization (RR 5.7; 95% CI 1.1e28.5)

* Corresponding author. Tel.: 34 932532141/32100; fax: 34 932033959; Mobile: 34 659415220. E-mail address: myurrea@yahoo.com (U.A. Mireya). 0163-4453/$30 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2006.03.023

Nosocomial infections in paediatric patients

213

and parenteral nutrition (RR 2.4; 95% CI 1.2e4.6). The hospital stay was higher in infected patients than in non-infected patients (p < 0.001). Conclusions: This study describes the epidemiological prole of NI in two high-risk paediatric units. These results suggest the need to evaluate the infection control measures with the aim of reducing associated morbidity. 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Introduction
Nosocomial infections (NI) are an important public health problem associated with substantial morbidity and mortality in high-risk units, prolonged hospital stays, and increased health care costs. Although the majority of the literature is based on adult patient studies, many of the risk factors associated with the development of NI are common to paediatric patients.1 The risk of NI in paediatric patients depends not only on their age, primary disease and associated comorbidities, but also on the invasive procedures commonly used in high-risk units.2,3 There have been various attempts in many countries to control NI, with the goal of lowering and stabilising the rates. This has required heightened awareness on the part of health care professionals, systematic surveillance of the incidence of infections, as well as the adoption of measures to control and prevent infection.4 The aim of this study is to describe the epidemiological prole of NI in the paediatric intensive care unit (PICU) and neonatal intensive care unit (NICU), its related risk factors and etiological microorganisms.

the second-line antibiotics are teicoplanin and meropenem. The NICU has 11 beds for intensive care, 20 for intermediate care and 10 for minimal care, with a mean annual admission rate of 524 newborns and an average daily occupancy rate of 80%. The nurse:patient ratio is 1:2. The standard rst-line antibiotics used in the NICU are teicoplanin or vancomycin and ceftazidime, and the second-line antibiotics are teicoplanin and meropenem.

Type of study, follow-up and denition of nosocomial infections

An observational prospective study included all patients admitted to the PICU and NICU during 6 months, from May to October 2000. A physician specialising in surveillance and control of hospital infections followed each patient daily from admission until hospital discharge. Inclusion criteria: patients admitted to the PICU or NICU with medical or surgical pathology for observation, diagnosis or treatment. Exclusion criteria: those patients whose stay in the PICU or NICU was less than 24 h, and patients hospitalised prior to the beginning of the study. Data were obtained from hospital charts, nursing notes and oral communication with the attending physicians. Information were recorded in a predened format that included demographic data, diagnoses, intrinsic risk factors, extrinsic risk factors, surgery, and NI data (site, date of onset, microbiological cultures). Intrinsic risk factors to take into account in the PICU included the following: coma, respiratory distress syndrome, renal failure, malnutrition, congenital malformations, diabetes mellitus, neoplasia and neutropenia. The Clinical Classication System (CCS)5 was used as a baseline measure of the patients clinical condition, according the following categories: class I (patients needing only routine hospital care), class II (physiologically stable patients admitted only for observation or monitoring), class III (patients who are physiologically stable but need ICU support), and class IV

Methods
Patients and setting
The Hospital Sant Joan de Deu is a 360-bed tertiary care paediatric hospital located in Barcelona. The PICU includes 14 beds for medical and surgical paediatric patients of all ages except neonates, and it has an average yearly admission rate of 650 and an average daily occupancy rate of 70%. General medicine, haematology/oncology, trauma, neurosurgery, cardiovascular surgery, gastrointestinal surgery, orthopaedic surgery, otorhinolaryngology surgery and stem cell transplantation are the most frequent health care subspecialties in the PICU. The nurse:patient ratio is 1:2e3. The standard rst-line antibiotics used in the PICU are teicoplanin and ceftazidime, and

214 (physiologically unstable patients needing assessment and intervention by ICU). In the NICU the intrinsic risk factors considered were as follows: birth weight, gestational age, and congenital malformations. Baseline risks used in relation to clinical prognosis were birth weight less than 1000 g and gestational age lower than 28 weeks. Extrinsic risk factors during hospitalisation included the following: urinary catheterization, peripheral or central venous catheterization, umbilical venous or arterial catheterization, arterial catheterization, parenteral nutrition and mechanical ventilation. Centers for Disease Control and Prevention (CDC)6 criteria were used as the standard denition for NI. Infections were regarded as nosocomial if they occurred 72 h after PICU or NICU admission.

U.A. Mireya et al. the CCS, 65.8% (169) were class II patients. The most frequent diagnosis on admission was medical pathology (35.4%): primarily convulsive syndrome, meningococcal sepsis and cardiac rhythm disorders, followed by surgical pathology (Table 1).

Table 1 PICU Age Gender Male Female CCS I II III IV

Demographic characteristics Mean (SD) or N (%) 7.5 years (6.1) 145 (56) 112 (44) 21 169 49 18 91 56 25 25 20 18 11 9 2 (8.2) (65.8) (19.1) (7.0) (35.4) (21.8) (9.7) (9.7) (7.8) (7.0) (4.3) (3.5) (0.8)

Patients characteristics

Statistical analysis
Infection rates were calculated as overall infection rate (per 100 admissions and 100 patient-days) and device-specic infection rate (per 100 deviceutilisation days). Denominators used to calculate the incidence of NI were the number of patients in the PICU and NICU, daily number of admissions, number of patient-days, number of urinary catheter days, number of ventilator days and number of central venous catheter days. Differences between patients with and without NI for discrete variables were estimated by the chi-square test or by Fishers exact test. In relation to continuous variables we used the Mann Whitney U-test. The association between risk factors and the presence of NI were estimated by crude and adjusted relative risk (RR) and their corresponding 95% CI. The Prentice Williams Peterson-Counting Process7 was the multivariable model used to analyse the interdependence between successive infections in the same patient and the effects of current and previous risk factors. The signicance level used was p less than 0.05. Statistical analysis was performed with SPSS (version 10.1) and S-PLUS 4.5. The categories compared in the model were those presenting the lowest rate of NI in the crude analysis.

Diagnosis Medical pathology Multiple trauma Cardiac surgery Orthopaedics surgery Neurosurgery Haematology/oncology Abdominal surgery Other surgerya Intoxication NICU Age Gender Male Female Birth weight (g) <1000 1000e1499 1500e2499 >2500 Weeks of gestation <28 29e32 33e36 >36 Diagnosis Hyaline membrane disease Congenital malformations Transitory newborn apnoea Prematurity Meconium aspiration Carcinogenesis Jaundice of prematurity
a

3.0 days (2.5) 74 (61) 47 (39) 19 21 29 52 17 22 33 49 45 39 14 12 7 2 2 (15.7) (17.4) (24.0) (43.0) (14.0) (18.2) (27.3) (40.5) (37.2) (32.2) (11.5) (9.9) (5.8) (1.7) (1.7)

Results
Patient characteristics
PICU Two hundred and fty-seven patients were included during the study period. With respect to

Maxilofacial surgery, otorhinolaryngology surgery.

Nosocomial infections in paediatric patients NICU One hundred and twenty-one newborns were included during the study period. Of the total patients 43% (52) weighed more than 2500 g and 40.5% (49) were born after 36 weeks of gestation. The most frequent diagnosis on admission was hyaline membrane disease (37.2%) (Table 1).

215 The most frequent microorganisms isolated were Gram-positive bacteria (49.2%), followed by Gram-negative microorganisms (43.4%) and Candida albicans (7.2%). The most common pathogens were coagulasenegative staphylococci (65.7%) in bacteraemia, Pseudomonas aeruginosa (28.5%) in lower respiratory tract infections, Escherichia coli (40%) in urinary tract infections, P. aeruginosa (40.0%) and Enterobacter cloacae (40.0%) in gastrointestinal infection (Table 2). NICU The most frequent NI episode was bacteraemia 59% (53), followed by conjunctivitis 20% (18) (Table 2). The microorganisms most frequently isolated were Gram-positive bacteria (71.1%), followed by Gram-negative bacteria (28.9%). The most common pathogens were coagulase-negative staphylococci (83.0%) in bacteraemia, P. aeruginosa (50.0%) in respiratory tract infections, E. coli (42.8%) in urinary tract infections, coagulase-negative staphylococci (61.1%) in conjunctivitis (Table 2).

Characteristics of nosocomial infections

PICU Of the patients admitted, 39 (15.2%) had an NI (30.8% had two or more episodes of NI). The rate of NI per 100 admissions was 26.5 and 1.75 per 100 patient-days. The largest proportion of NI was a detected inpatient with surgery for abdominal pathology 27.2% (3 patients), cardiac surgery 20% (5) and multiple trauma 17.8% (10). With respect to CCS, 45.1% (8) of the class IV patients presented at least one episode of infection, followed by 36.7% (18) of the class III patients, and 7.7% (13) of the class II patients. Class I patients did not present any episode of NI. NICU Of the neonates admitted, 56 (46.3%) developed an NI (35.7% had two or more episodes of NI). The rate of NI was 74.3 infections per 100 admissions and 2.7 infections per 100 patient-days. The largest proportion of patients with an episode of NI consisted of neonates with meconium aspiration 71.4% (5 neonates), hyaline membrane disease 51.1% (23) and congenital cardiopathy 47.3% (9). The 68.4% (13) of neonates weighing less than 1000 g presented at least one episode of infection, as did 42.8% (9) of neonates weighing 1000e 1499 g, 51.7% (15) of neonates weighing 1500e 2499 g and 36.5% (19) of neonates weighing more than 2500 g. Of the neonates born at less than 28 weeks of gestation, 64.7% (11) presented an episode of NI; 36.3% (8) of those born between 29 and 32 weeks of gestation; 57.5% (19) between 33 and 36 weeks of gestation and 36.7% (18) of those born after 36 weeks of gestation.

Nosocomial infection and risk factors

PICU Patients with CVC had the highest rate of bacteraemia (2.5 bacteraemias per 100 device-days), followed by 1.8 bacteraemias per 100 devicedays in-patients with parenteral nutrition. The rate of respiratory infection in-patients with mechanical ventilation was 1.6 per 100 device-days, and the rate of urinary tract infection in-patients with urinary catheterization was 0.9 per 100 device-days. The risk factors most closely associated with the development of NI were age under 1 year (RR 5.0; 95% CI 1.6e15.4), class IV of CCS (RR 3.7; 95% CI 1.2e11.1) and mechanical ventilation (RR 2.5; 95% CI 1.0e6.0) (Table 3). NICU Neonates with umbilical arterial catheterization had the highest rates of bacteraemia (14.2 bacteraemias per 100 device-days), followed by 4.4 bacteraemias per 100 device-days in-patients with parenteral nutrition. The rate of respiratory infection in neonates with mechanical ventilation was 1.5 per 100 device-days, and the rate of urinary tract infection in neonates with urinary catheterization was 1.2 per 100 device-days. The risk factors most closely associated with the development of NI were birth weight less than 1000 g (RR 2.8; 95% CI 1.0e8.0), umbilical arterial

Site of infection and pathogen distribution of nosocomial infections

PICU The most frequent NI episode was bacteraemia 51.5% (35), followed by lower respiratory tract infection 20.6% (14), of which 78.5% were cases of pneumonia associated with mechanical ventilation (Table 2).

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Table 2

Distribution of NI by site and frequency (%) of pathogens aisled Type of infection BACT PICU NICU LRTI PICU NICU UTI PICU NICU GI PICU NICU SWI PICU SKIN NICU PICU NICU CONJ NCIU (40.6) 60 (66.6) (3.0) 1 (1.1) (2.9) (1.4) 3 (3.3) (23.2) (8.6) (7.2) (2.9) (1.4) 4 (4.4) 12 (13.3) 8 (8.8) 2 (2.2) Care unit PICU NICU

Gram-positive cocci CNS Staphylococcus aureus Streptococcus spp. Enterococcus spp. Gram-negative bacillus Pseudomonas aeruginosa Escherichia coli Enterobacter cloacae Enterobacter spp. Klebsiella spp. Yeasts Candida albicans Total

23 (65.7) 44 (83.0) 2 (14.3) 2 (25.0) 1 (2.8) 1 (1.8) 2 (14.3) 2 (14.3) 1 (2.8) 2 (3.7) 5 1 2 4 1

2 (28.5) 1 (20.0) 1 (33.3) 1 (50.0)

1 (14.2)

1 (50.0) 1 (100) 10 (61.1) 28 3 2 1 16 6 (27.7) 6 5 2 (11.1) 2 1 1 (50.0)

(14.2) 4 (28.5) 4 (50.0) 3 (30.0) 2 (40.0) 1 (50.0) (2.8) 2 (3.7) 1 (7.1) 4 (40.0) 3 (42.8) 1 (33.3) (5.7) 1 (10.0) 2 (40.0) 4 (7.5) 2 (14.3) 1 (12.5) 1 (14.2) (2.8) 1 (12.5) 1 (33.3) 1 (7.1) 53 14 8 2 (20.0) 10 7 5 3 2

1 (2.8) 35

5 (7.2) 1 18 69 90

CNS: coagulase-negative Staphylococcus; BACT: bacteraemia; LRTI: lower respiratory tract infection; UTI: urinary tract infection; GI: gastrointestinal infection; SWI: surgical wound infection; CONJ: conjunctiva infection; PICU: paediatric intensive care unit; NICU: neonatal intensive care unit.

U.A. Mireya et al.

Nosocomial infections in paediatric patients

Table 3 Risk factors of NI in the PICU RR c (95% CI) 1.8 1.5 1.3 2.1 4.4 5.8 2.3 4.8 3.7 4.2 2.0 2.9 (0.7e4.5) (0.5e4.2) (0.5e3.4) (0.7e5.6) (2.2e8.7) (2.6e12.8) (1.3e4.0) (2.2e10.3) (2.2e6.1) (2.4e7.4) (1.0e4.0) (1.7e4.9) RR a (95% CI) 5.0 2.6 1.5 3.8 2.5 3.7 2.9 16.0 2.2 2.5 2.0 2.3

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Risk factors Age (years) <1 1e5 11e15 >15 Clinical classication system III. Stable IV. Unstable Coma Renal failure Central venous catheter Mechanical ventilation Parenteral nutrition Urinary catheter

(1.6e15.4) (0.8e8.4) (0.7e3.0) (1.2e11.7) (1.1e5.5) (1.2e11.1) (1.4e6.0) (5.6e45.6) (1.0e4.6) (1.0e6.0) (1.0e3.6) (0.7e7.8)

RR c: Crude Relative Risk, RR a: Adjusted Relative Risk. Comparison categories: age between 6 and 10 years, CCS class II, absence of extrinsic risk factors.

catheterization (RR 5.7; 95% CI 1.1e28.5) and parenteral nutrition (RR 2.4; 95% CI 1.2e4.6) (Table 4).

Distribution of nosocomial infection by length of stay

PICU The median hospital stay was 10 days (range 7e16 days). Infected patients had signicant longer median hospital stays 22 days (range 15e37 days) than non-infected patients 9 days (range 6e14 days) (p < 0.001). The presence of any episode of NI prolonged the period of hospitalisation by an average of 21 days (SD 20.4) (p < 0.05). For the most frequently occurring types of infection, the mean hospital stay from admission to discharge was as follows: bacteraemia 21.3 days (SD 25.1), respiratory tract infection 42.1 days (SD 31.7), and urinary tract infection 30.3 days (SD 37.7).

NICU The median hospital stay was 17 days (range 8e36 days). Infected patients had signicant longer median hospital stays 30.5 days (range 20e65 days) than non-infected patients 9 days (range 6e16 days) (p < 0.0001). The presence of any episode of NI prolonged hospital stays by an average of 29.4 days (SD 20) (p < 0.05). For the most frequently occurring types of infection, the average hospital stay from admission to discharge was as follows: bacteraemia 42.7 days (SD 32.9), conjunctivitis 28.7 days (SD 18.3), and respiratory tract infection 21.8 days (SD 14.0).

Discussion
This study provides information on the epidemiology of nosocomial infections, enabling us to establish

Table 4

Risk factors of NI in the NICU RR c (95% CI) 2.2 1.3 1.5 1.8 2.0 3.1 1.4 12.8 (1.1e4.3) (0.6e2.5) (0.7e2.9) (1.1e2.8) (1.2e3.2) (1.9e5.1) (0.7e2.8) (2.7e58.7) RR a (95% CI) 2.8 1.6 1.8 1.6 0.9 2.4 1.1 5.7 (1.0e8.0) (0.7e3.3) (0.8e3.7) (1.0e2.6) (0.5e1.6) (1.2e4.6) (0.6e2.0) (1.1e28.5)

Risk factors Weight (g) <1000 1500e2500 >2500 Central venous catheter of peripheral insertion Mechanical ventilation Parenteral nutrition Urinary catheter Umbilical arterial catheter

RR c: crude relative risk, RR a: adjusted relative risk. Comparison categories: birth weight between 1000 and 1499 g, absence of extrinsic risk factors.

218 the incidence rate, distribution, and pathogenic association, as well as the risk factors associated in our PICU and NICU. Observational epidemiological studies yield a great deal of useful information about the impact of NI in high-risk hospital services, making it possible to establish cause and effect relationships and associations between risk factors intrinsic to the patients and those resulting from diagnostic and therapeutic interventions required during the period of hospitalisation.8 Some of these factors are considered modiable or subject to some degree of control, and this may signicantly reduce the incidence of infections and their associated complications. Most of the data on NI described in the literature come from the paediatric or neonatal services of general hospitals.9,10 These articles focus on the most common types of infection or on epidemic outbreaks of Enterobacter spp. and coagulasenegative staphylococci, among others.11e13 The epidemiological prole of NI in PICU and NICU has been described in some studies published in international journals,2,3,14,15 but in Spain there are few published observational studies on this subject.16e18 Rates of NI incidence in our hospital are considered high in relation to international standards. Observational studies carried out in the United States in recent decades record NI incidence rates between 4.8% and 11% in PICU 15,19,20,23 and between 5.9% and 24.6% in NICU.14,21e23 Differences may be partially explained by the methodology used, especially in relation to the duration of the study, since in most of the published studies the minimum follow-up period is one year, and in our study the follow-up was 6 months.9,10,19 Additionally, Spanish hospitals lack a frame of reference of the type provided to U.S. hospitals by the National Nosocomial Infections Surveillance (NNIS) system report, published periodically by the Centers for Disease Control and Prevention.23 The NNIS system, the most important multicentric study currently being carried out in the US, shows overall rates of infection in paediatric patients of 1.47 infections per 100 patient-days.23 The NNIS reports infection rates by type of infection and by association with extrinsic factors in different intensive care units, including paediatric units, without making a distinction between PICU and NICU. For this reason our results cannot be compared directly with those of the NNIS. The distribution pattern of NI by site observed in our study coincides with the observations of Richards et al.,2 Singh-Naz et al.,19 and Mager et al.20 There may be some variability in relation

U.A. Mireya et al. to concomitant outbreaks or epidemic infections, but this situation did not arise during the study period in our hospital. It is striking that conjunctivitis is the second most common NICU infection. The high percentage of coagulase-negative staphylococci isolated suggests that this may result from repeated handling of these patients by health professionals who do not wash their hands as frequently as recommended, or it may also be an artefact of the intensity of surveillance activities. The distribution of pathogens is in agreement with the literature available on NICU14,22,24 and PICU.2,9,10 Actually it has become evident that coagulase-negative staphylococci are an important cause of NI also in paediatric patients. Given that the most frequent types of infection are bacteraemias, it is to be expected that this is the microorganism most often isolated. Another microorganism frequently isolated in neonatal and paediatric intensive care units is Enterobacter spp.,1,21,22 particularly in low birth weight and premature infants. The principal mechanism by which this microorganism is disseminated is cross-transmission by hands or manipulation of nursing staff.13 The NI rates observed by days of exposure to extrinsic risk factors compared with the NNIS results are above the 90th percentile.23 This may be explained by the development and active implementation of guidelines for the prevention and control of infections during the past decade in the United States, which have made possible the reduction of NI and their associated complications. In Spain important progress has been made in raising the awareness of health professionals concerning the correct use of infection control measures, but the level of compliance on a regular basis is probably lower than in the United States. Premature and low birth weight infants constitute a population at signicant risk for developing infections, and our data coincide with those published by Stoll et al.,21 Makhoul et al.,25 and Brodie et al.14 The risk of NI is inversely related to birth weight and gestational age at birth.26 Another factor to consider is the length of hospital stay. Patients who develop an NI tend to remain in the hospital longer than those without it, as other studies have also found.1,21,27 It is important to keep in mind that other factors interact with length of hospital stay, such as the patients underlying clinical condition, associated comorbidities, and the type of treatment used. Any and all of these may increase the risk of infection, and prolong the period of hospitalisation. Our results strongly suggest the need to improve measures of prevention and control of NI, without

Nosocomial infections in paediatric patients losing sight of the fact that the single most important and simplest of these measures is frequent hand washing, as well as limited use of antibiotics. Efforts to control the incidence of infection should be aimed at preventable factors, in many cases associated with external or invasive medical devices, principally through restricted use and early withdrawal, the use of adequate antiseptic, and techniques during insertion, manipulation and maintenance.28e31 This study describes the epidemiological prole of nosocomial infections in two high-risk paediatric units. The knowledge of the frequency and distribution of these infections in hospital environments and their association with factors that can be controlled is a necessary rst step in reducing the risk of NI and their associated morbidity and mortality.

219
9. Vermaat JH, Rosebrugh E, Ford-Jones EL, Ciano J, Kobayashi J, Miller G. An epidemiologic study of nosocomial infections in a pediatric long-term cares facility. Am J Infect Control 1993;21:183e8. 10. Jarvis WR, Edwards JR, Culver DH, Hughes JM, Horan TC, Emori TG, et al. Nosocomial infection rates in adult and pediatric intensive care units in the United States. Am J Med 1991;Suppl. 3B:185Se91S. 11. Shah S, Ehrenkranz RA, Gallagher PG. Increasing incidence of Gram-negative rod bacteremia in a newborn intensive care unit. Pediatr Infect Dis J 1999;18:591e5. 12. Saiman L, Ludington E, Pfaller M, Rangel-Frausto S, Wiblin T, Dawson J, et al. Risk factors for candidemia in neonatal intensive care unit patients. Pediatr Infect Dis J 2000;19:319e24. 13. Hervas JA, Ballesteros F, Alomar A, Gil J, Benedi VJ, Alberti S. Increase of Enterobacter in neonatal sepsis: a twenty-two-year study. Pediatr Infect Dis J 2001;20: 134e40. 14. Brodie SB, Sands KE, Gray JE, Parker RA, Goldmann DA, Davis RB, et al. Occurrence of nosocomial bloodstream infections in six neonatal intensive care units. Pediatr Infect Dis J 2000;19:56e62. 15. Ruza F, Alvarado F, Herruzo R, Delgado MA, Garcia S, Dorao P, et al. Prevention of nosocomial infection in a pediatric intensive care unit (PICU) through the use of selective digestive decontamination. Eur J Epidemiol 1998;14: 719e27. 16. Herruzo R, Garc J, Garc P, del Pino Gil M, Gomez M, a a del Rey J. Nosocomial infection and its impact on the study in a neonatal intensive care unit (1988e1991). Rev Sanid Hig blica (Madr) 1993;67:153e63. Pu 17. Saleta JL, Rosales M, Dom nguez V, Jimenez T, Marian J, Bouzas ME. Incidence and risk factors for nosocomial infections in a neonatology unit. Enferm Infecc Microbiol Clin 1996;14:357e60. 18. Munoz E, Herruzo R, Garcia J, Fernandez M, Quero J. Nosoco mial infection over three years in a neonatal intensive care unit. Multivariate study. Med Clin (Barc) 1997;109:527e31. 19. Singh-Naz N, Sprague BM, Patel KM, Pollack MM. Risk factors for nosocomial infection in critically ill children: a prospective cohort study. Crit Care Med 1996;24:875e8. 20. Mager G, Kitzinger K, Poveda S. Preventing nosocomial infections in hospitals. Sci Am 2001;285:86e90. 21. Stoll BJ, Hansen N, Fanarof AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002;10:285e91. 22. Gaynes RP, Martone WJ, Culver DH, Emori TG, Horan TC, Banerjee SN, et al. Comparison of rates of nosocomial infections in neonatal intensive care units in the United States. Am J of Med 1991;91(Suppl. 3B):192Se6S. 23. National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1992eJune 2001, issued August 2001. Am J Infect Control 2000;29:404e21. 24. Gaynes RP, Edwards JR, Jarvis WR, Culver DH, Tolson JS, Martone WJ, The National Nosocomial Infections Surveillance System. Nosocomial infections among neonates in high-risk nurseries in the United States. Pediatrics 1996; 98:357e61. 25. Makhoul IR, Sujov P, Smolkin T, Lusky A, Reichman B. Epidemiological, clinical and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey. Pediatrics 2002;109:34e9. 26. Mullet MD, Cook FE, Gallagher R. Nosocomial sepsis in the neonatal intensive care unit. J Perinatol 1998;18: 112e5.

Acknowledgments
We wish to thank the NICU and PICU nurses at the Hospital Sant Joan de Deu for their co-operation. Susan M. DiGiacomo, Ph.D., of the Fundacio Sant Joan de Deu, prepared the English-language ver sion of the manuscript.

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