Prevention and Treatment of Nosocomial Sepsis in the NICU


Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. Thus, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a “real” blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of “proven” sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to describe simple changes in process, which when implemented, can reduce nosocomial infection rates in neonates and improve outcomes.


Effective strategies to prevent nosocomial sepsis must include continuous monitoring and surveillance of infection rates and distribution of pathogens; strategic nursery design and staffing; emphasis on staff accountability for incidence of nosocomial infections; programs to increase emphasis on hand-washing compliance; cautious insertion and handling of central venous catheters; minimizing central venous catheter duration; and prudent use of antimicrobial agents. Educational programs and feedback to NICU personnel improve compliance with infection control programs.1

Hand Hygiene

The simplest strategy for decreasing nosocomial sepsis and the most difficult with which to achieve compliance is good hand hygiene.2, 3, 4, 5, 6 The rationale for hand washing is to reduce transient and resident microflora.7, 8, 9, 10, 11, 12, 13, 14 Several hand-washing products have been studied. The residual effect of chlorhexidine gluconate and Triclosan® appear to provide an advantage over other disinfectants.13, 15, 16, 17 Waterless alcohol products are equally effective in initial antisepsis and improve compliance.18, 19, 20 Ensuring that hand-washing techniques13, 17 (duration of wash, type of soap) are appropriate is important. In addition, locating hand-washing opportunities close to the site of care improves compliance and reduces the risk of crosscontamination. Several controlled trials of hand washing demonstrate that it is effective at reducing nosocomial infections.8, 21, 22, 23, 24, 25

Compliance with hand washing can be improved by reducing barriers19, 20, 21, 26, 27, 28, 29 and actively promoting compliance.17, 18, 19, 20, 30 Defining specific policies, which eliminate hand-related artificial fingernails and hand jewelry that spread infection, can help reduce infection rates. Several studies have shown that Pseudomonas outbreaks have been associated with long and artificial nails.31, 32 Artificial nails are also more often colonized with pathogenic organisms than natural nails.33, 34

Use of Human-milk Feedings

In a prospective controlled trial, neonates fed breast milk were less likely to become septic compared to formula-fed neonates.35 Hylander et al.36 showed that human-milk feedings reduced the odds of sepsis/meningitis compared to preterm milk feedings (OR=0.43; 95% CI: 0.23 to 0.81). The efficacy of breast milk also appears to be dose dependent and neonates for whom breast milk is the primary source of nutrition have fewer episodes of infection than when breast milk is only a small part of the daily nutrition.37

Intravenous Immunoglobulin

Meta-analysis of clinical trials in low-birth-weight neonates shows that prophylactic intravenous immunoglobulin administration resulted in a significant reduction in sepsis (clinical signs and symptoms of sepsis and positive blood culture for bacteria or fungi decreased by 3%) and the occurrence of serious infection (clinical signs and symptoms in conjunction with positive cultures from blood, cerebrospinal fluid, urine was decreased by 4%).38 However, the use of intravenous immunoglobulin is not associated with improvement in other important outcomes (necrotizing enterocolitis, intraventricular hemorrhage, or length of hospital stay); therefore, most authors do not recommend routine use of intravenous immunoglobulin to prevent nosocomial sepsis.38, 39, 40

NICU Design

Several design factors may reduce the incidence of nosocomial sepsis. Overcrowding, inadequate design of sinks and soap containers, inconvenient placement of supplies, improper maintenance of surface-covering materials (e.g., carpet), and poorly designed air flow/isolation facilities can also increase the occurrence of neonatal sepsis. Elements of a well-designed NICU, with respect to reduction of nosocomial infection, include: 120 to 180 ft2 per bed space, sinks within 20 ft of each bed, and having all commonly used equipment easily accessible at each bedside. Each NICU needs at least one isolation room with enough space for two commonly infected babies and an area for hand washing, gowning, and storage of clean and soiled materials located directly outside or immediately inside the entry door to the room.41 It is important to remember that good designs are of little value without good policies, and bad designs can largely be rescued with good policies.

Reducing Intravascular Line-Related Infections

Line and line-connection contamination

Catheter-related sepsis has been shown to result from entry of microbes extraluminally via the skin at the insertion site and through the catheter hub after colonization of the hub during repeated manipulations.42, 43 Sepsis appearing within a short time period after catheter insertion is usually from skin contamination, while hub colonization results in bloodstream infection occurring after the first week of line duration. The same microorganism is often isolated from both the patient's skin and the catheter hub. This suggests that the health-care provider's hands may transfer skin flora to the inner surface of the catheter hub during hub manipulation and replacement of the infusion set and emphasizes the importance of good hand hygiene.44, 45, 46, 47

The design of line setups can influence the risk of infection and reducing the number of ports, decreasing the use of three-way stopcocks, and limiting the number of catheter lumens may decrease the occurrence of line sepsis.46, 47 Strategies that reduce the likelihood of line sepsis include: minimizing blood sampling by batching laboratory specimen draws;48 prepping of hubs with disinfectants;44, 49 use of an alternative hub design with an antiseptic chamber;50, 51, 52 and use of better hub connectors with needleless systems.

Line insertion

How the line is placed is equally important. Choosing a good site will reduce the number of percutaneous sticks required for successful placement of the line and decrease the likelihood of line contamination during the process. The skin should be carefully prepped before line placement. Available prep solutions include alcohol, povidone-iodine, and chlorhexidine gluconate. Garland et al.53 compared the efficacy of 0.5% chlorhexidine gluconate in 70% isopropyl alcohol to povidone-iodine in a nonrandomized prospective study in neonates. Chlorhexidine gluconate antisepsis was associated with decreased peripheral intravenous catheter colonization. In a prospective randomized trial of povidone-iodine, alcohol, and chlorhexidine gluconate in a surgical intensive care unit, chlorhexidine gluconate was associated with the lowest incidences of local catheter-related infection and bacteremia.54 The new guidelines from the US Department of Health and Human Services Centers for Disease Control suggest that 2% chlorhexidine gluconate-containing solutions are the agent of first choice in skin antisepsis for line insertion.42, 43

While placing a central venous catheter, the use of gown and gloves are both important. The concept of maximal barrier precautions stipulates the use of sterile cap, mask, gown, gloves, and drape. The rationale for this procedure is the reduction of contamination during the insertion process of the indwelling catheter. The benefits of this procedure have been demonstrated in prospective randomized trials in adult critical care patients.55, 56

Reducing the time the central line catheter is in place

The best method for reducing the risk of line infections is to reduce the duration of time that the central catheter is used.42, 43 Several studies show a direct correlation between the use and duration of deep lines and the incidence of sepsis in neonates.1, 57, 58, 59 In the largest of the studies, Chathas et al60 showed a critical time of 21 days, after which the risk for sepsis became significant. Most very-low-birth-weight infants will be close to full enteral calories by 21 days of age; thus, removing the central lines by 21 days is feasible. Introduction of early feedings with breast milk, consistent advancing of feeding volumes, and deciding to remove the deep lines in some infants before full enteral calories are introduced are important proactive strategies that can be used to reduce the risk of line sepsis.61, 62

Vancomycin prophylaxis for central lines

In meta-analysis, prophylactic use of vancomycin reduced blood-stream infection rates. In all five randomized-controlled trials reviewed, a decrease in the incidence of overall sepsis events and coagulase-negative Staphylococci sepsis events was reported. The authors conclude, however, that the clinical benefits are minimal and do not justify routine use of vancomycin prophylaxis.63 In addition, the risk of developing vancomycin resistance could not be conclusively disproved,63 and remains a concern with all strategies of prophylaxis with antimicrobial agents. Vancomycin-resistant enterococci are emerging as a serious problem, especially in immune-compromised patients and those admitted for intensive care.64, 65

Surface-coated central catheters

In adults, use of heparin-bonded central venous catheters reduced the nosocomial infection rate by 88%.66 Other materials that reduce bacterial adherence and the risk of colonization, when bonded to central venous catheters, include salicylic acid,43 silver,67, 68 and the glycopeptide, teicoplanin.69 Antiseptic bonding may also decrease the incidence of blood-stream infection. Agents used include cefazolin,70 iodine,71, 72 minocycline-rifampin73 and chlorhexidine-silver-sulfadiazine.74 Of note, none of these studies has involved neonates.43, 73, 74, 75, 76, 77 Until clinical studies documenting the efficacy, safety, and absence of emergence of antibiotic resistance in neonates are carried out, routine clinical use of catheters with antiseptic coatings is not warranted in the NICU.43

Removing the line when there is a positive culture

The outcome for patients whose central catheter is not removed after identification of pathogenic bacteria is worse than it is for those patients whose catheters are removed promptly.78, 79 One positive blood culture for Staphylococcus aureus or a Gram-negative rod warrants immediate central line removal in a neonate.78 In neonates who have just one positive central line culture for coagulase-negative Staphylococci, clinicians may attempt medical management without central catheter removal, but documentation of subsequent negative blood cultures is crucial.78, 79, 80, 81 In neonates who have four consecutive positive cultures or 4 or more days of positive cultures for coagulase-negative Staphylococci, the likelihood of successfully clearing the line is low78, 80 and, in some studies, there is evidence that the risk of end organ damage and poor outcome is high.78

Managing Process

Bloom et al.82 evaluated the performance of 52 NICUs on acquired infection, identified higher and lower centers, contrasted their processes, and isolated meaningful differences. Eight high and eight low centers were observed using the observation guide written from this rigorous evaluation process. The network average was 3.4 episodes/1000 patient days. The average of the high centers was 10.4 episodes/1000 patient days and the average of the low centers was 0.5 episodes/1000 patient days. In all, 15 meaningful differences were isolated. For example, "low" infection rate centers used two people or a closed endotracheal suction system and Tenderfoot® auto lancets for lab sampling; washed hands prior to each patient interaction; and had the intent to limit days for intravenous, central venous, and umbilical lines. In contrast, "high" infection rate centers used an open system for endotracheal suctioning, hand-held lancets, and gloves as a substitute for hand washing, and had no focus on a time limit for I.V.s, central or umbilical lines. These data suggest that simple process changes can reduce the occurrence of nosocomial sepsis.


While changes in process can reduce the frequency of nosocomial infection, a number of different approaches and processes have been studied and were not found to influence the occurrence of nosocomial infections. Ventilator circuit changes more often than one time per week were not associated with a decrease in pneumonia or sepsis.83 Changing the frequency of tracheal suctioning from every 4 hours to every 8 hours did not change pneumonia or blood-stream infection rate.84 In addition, the use of closed tracheal suctioning had no effect on the incidence of nosocomial pneumonia, when compared with the open-suction method in intensive care unit patients, and actually increased the incidence of tracheal colonization versus open circuit.85 A study in neonates also showed no benefit with regard to a reduction in infections.84 Gowning before entering the NICU has no effect on reducing nosocomial infection.86, 87, 88 Infusion of fresh-frozen plasma increased immunoglobulin G levels, but did not improve bacterial opsonification or decrease infection rates.89, 90, 91 Maintaining skin integrity is important, but overuse of emollients can increase the risk of infection.92, 93, 94, 95


Who to Treat

Determining whom to treat and for how long are difficult clinical decisions and there is no consensus on how to establish as to who has life-threatening sepsis. While some authors report that inflammatory markers (interleukin-6,96, 97, 98 interleukin-8;99, 100, 101, 102, 103, 104, 105, 106 and C-reactive protein96, 107, 108, 109, 110, 111, 112) change with acquired infection in the premature infant, only two articles have suggested a laboratory methodology that could be used to decrease antibiotic exposure on the basis of specific criteria.104, 105

Antibiotic Choice

A specific antibiotic choice must be driven by hospital-specific guidelines based on the major causes of nosocomial sepsis and organism susceptibility patterns in that specific hospital. However, it is equally important to recognize that our choice of antimicrobial agents influences the types of neonatal sepsis and their antibiotic resistance patterns. De Man et al.113 investigated whether the emergence of resistant strains could be halted by modifying empirical antibiotic regimens. The authors assigned two similar NICUs to different empirical antibiotic regimens. In one NICU, penicillin G and tobramycin were used for early-onset septicemia; flucloxacillin and tobramycin were used for late-onset septicemia; and no broad-spectrum beta-lactam antibiotics, such as amoxicillin and cefotaxime, were used. In the other NICU, intravenous amoxicillin with cefotaxime was the empirical therapy. The relative risk for colonization with strains resistant to the empirical therapy was 18 times higher for the amoxicillin–cefotaxime regimen compared with the penicillin–tobramycin regimen (95% CI 5.6 to 58.0, p<0.01). The authors concluded that a regimen avoiding amoxicillin and cefotaxime reduces the resistance problem.113

A second common problem in the NICU is the overuse of vancomycin.114, 115 Stoll et al.,115 studying very low birth-weight neonates (401 to 1500 g), found that 56% of 6215 infants received at least one course of antibiotics started after day 3 of birth and 44% were treated with a course of vancomycin. Vancomycin use was inversely related to birth weight (401 to 500 g, 78%; 501 to 750 g, 75%; 751 to 1000 g, 60%; 1001 to 1250 g, 36%; 1251 to 1500 g, 18%). Interestingly, 30% of patients without culture-proven infection also received this drug.115

The question that remains to be answered is whether it is safe NOT to prescribe vancomycin at the time of the initial workup. Karlowicz et al.116 showed that coagulase-negative Staphylococcus is rarely fulminant and the mortality rate among neonates with coagulase-negative Staphylococci is no different from uninfected neonates.115 It may be reasonable to consider treating stable neonates with oxacillin or nafcillin instead of vancomycin for the 24 to 48 hours that it takes to identify a positive culture for coagulase-negative Staphylococci, but this approach should be subjected to prospective study before being utilized.116

An equally important issue is what antibiotics should be chosen to cover for the Gram-negative organisms — amikacin, tobramycin, or cephalosporin. Overuse of cephalosporins has been associated with the emergence of resistant organisms113 and higher rates of fungal infections.117 The current recommendation is to use an aminoglycoside in combination with oxacillin or nafcillin as Gram-positive coverage for neonates with suspected and not-yet-proven sepsis.

Duration of Treatment

Improved culture media and new technology integrated into blood culture systems have shortened the incubation time required to detect positive culture results. Investigators have shown a 97% to 100% yield at 48 hours for positivity of blood cultures.118, 119, 120, 121, 122, 123, 124, 125 These data suggest that in the absence of clinical signs of sepsis, which suggest that the blood culture is falsely negative, antibiotics can be stopped after 48 hours of treatment, if the blood culture is negative.

The best way to reduce the overuse of antibiotics in the NICU is to establish protocols that lead to the appropriate stopping of antibiotics in neonates whose cultures are negative and who have no evidence of sepsis after a 48-hour course of therapy.



The incidence of candidemia is rising steadily, and Candida species are a leading cause of infectious mortality in the NICU.58, 115, 117, 126, 127, 128, 129 The cumulative incidence of candidemia in extremely low-birth-weight (<1000 g) infants is 4% to 15%.115, 117, 128 Candida blood-stream infection is associated with an attributable mortality of 38% and a crude mortality of 30% to 75%.58, 115, 117, 126, 127, 128, 129 Prompt diagnosis and initiation of antifungal therapy are crucial to survival across patient populations.117

Like other etiologies of neonatal sepsis, the current gold standard for the diagnosis of neonatal candidiasis is the blood culture. Unfortunately, while the blood culture is sensitive for bacterial pathogens, it is a poor diagnostic tool for invasive candidiasis. From animal models, the sensitivity of the blood culture to diagnose catheter-related candidemia and acute, disseminated, overwhelming candidiasis is approximately 80%, but the sensitivity of blood culture for transient candidemia is below 50%.130, 131 Data from autopsy studies indicate that the sensitivity of blood cultures to diagnose chronic disseminated and deep organ candidiasis is less than 50%.132, 133, 134, 135 Previous analyses of incidence and attributed mortality of neonatal candidiasis are based on the use of candidemia as equivalent to invasive candidiasis and may be misleading. Neonatal candidiasis diagnosed by blood-culture techniques underestimates the burden of disease.132, 133, 134, 136


There are two studies evaluating antifungal prophylaxis.128, 129 There have been no trials examining presumptive therapy or comparing prophylaxis with presumptive therapy. One of the two trials evaluating prophylaxis did not show substantial benefit.129) Rectal colonization was decreased, but infection rates were not changed. The other trial showed benefit, but the control group (N=50) had a very high rate of neonatal candidiasis — 18%. This rate of systemic candidal infection was higher than reported previously.129 Both of these studies were single-center studies that enrolled small numbers of neonates (N=100,128 and N=103,129 respectively). A high rate of the primary end point in the control group in a small single-center study suggests that the degree of estimated effect may be an overestimate.137

In general, prophylaxis exposes far more patients with much greater cumulative doses of antimicrobial agents than empirical therapy does. Antifungal prophylaxis, in those populations where it is currently indicated (patients who have received stem-cell transplantation, for example), reduces, but does not eliminate, invasive fungal infections, and in those children who receive antifungal prophylaxis, empirical antifungal therapy continues to show benefit.137


The primary modes of treatment are removal of any lines that are the source of infection, amphotericin, and 5-fluorocytosine in neonates with central nervous system involvement.138 Since the diagnosis of Candida sepsis is difficult to make, some authors suggest empirical therapy for high-risk neonates.117 End-organ evaluation of the neonate should include a lumbar puncture, echocardiogram, abdominal ultrasound, and ophthalmologic exam as these can influence the length of therapy and prognosis.139


Nosocomial sepsis is a serious and common problem for neonates who are admitted for intensive care because it is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. It is, therefore, critically important to look for simple changes in processes of care (reducing barriers to hand washing, developing careful protocols for limiting the duration and contamination of central lines, improving the design of the NICU, and early feedings), which, when implemented, can help reduce the risk of nosocomial sepsis and improve outcomes.


  1. 1

    Adams-Chapman I, Stoll BJ . Prevention of nosocomial infections in the neonatal intensive care unit. Curr Opin Pediatr 2002;14(2):157–164.

    PubMed  Google Scholar 

  2. 2

    Boyce JM, Rotter ML . Hospital hygiene procedures: areas of consensus and ongoing controversies. Proceedings of the 6th International BODE Hygiene Days 7–10 September 2000, Vienna, Austria. J Hosp Infect 2001;48(Suppl A): S1–S92.

    PubMed  Google Scholar 

  3. 3

    Boyce JM . Consequences of inaction: importance of infection control practices. Clin Infect Dis 2001;33(Suppl 3):S133–S137.

    PubMed  Google Scholar 

  4. 4

    Boyce JM . Antiseptic technology: access, affordability, and acceptance. Emerg Infect Dis 2001;7(2):231–233.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    Boyce JM . Using alcohol for hand antisepsis: dispelling old myths. Infect Control Hosp Epidemiol 2000;21(7):438–441.

    CAS  PubMed  Google Scholar 

  6. 6

    Boyce JM . It is time for action: improving hand hygiene in hospitals. Ann Intern Med 1999;130(2):153–155.

    CAS  PubMed  Google Scholar 

  7. 7

    Ehrenkranz NJ, Sanders CC, Eckert-Schollenberger D . et al. Lack of evidence of efficacy of cohorting nursing personnel in a neonatal intensive care unit to prevent contact spread of bacteria: an experimental study. Pediatr Infect Dis J 1992;11(2):105–113.

    CAS  PubMed  Google Scholar 

  8. 8

    Ehrenkranz NJ . Bland soap handwash or hand antisepsis? The pressing need for clarity. Infect Control Hosp Epidemiol 1992;13(5):299–301.

    CAS  PubMed  Google Scholar 

  9. 9

    Gould D . Infection control. Making sense of hand hygiene. Nurs Times 1994;90(30):63–64.

    CAS  PubMed  Google Scholar 

  10. 10

    Perraud M, Amazian K, Girard R, Tissot GF . The use of hand hygiene products could reduce colonization on the hands. J Hosp Infect 2001;47(4):336–337.

    CAS  PubMed  Google Scholar 

  11. 11

    Handwashing agents. Infect Control 1987;8(9):384–385.

  12. 12

    Rahman M, Chattopadhyay B . Handwashing: unanswered questions and compliance. J Hosp Infect 2000;45(3):249–250.

    CAS  PubMed  Google Scholar 

  13. 13

    CDC. Draft Guideline for Hand Hygiene in Healthcare Settings. CDC; 2002, Elsevier: England.

  14. 14

    Dharan S, Mourouga P, Copin P, Bessmer G, Tschanz B, Pittet D . Routine disinfection of patients' environmental surfaces. Myth or reality? J Hosp Infect 1999;42(2):113–117.

    CAS  PubMed  Google Scholar 

  15. 15

    Ayliffe GA, Babb JR, Davies JG, Lilly HA . Hand disinfection: a comparison of various agents in laboratory and ward studies. J Hosp Infect 1988;11(3):226–243.

    CAS  PubMed  Google Scholar 

  16. 16

    Kjolen H, Andersen BM . Handwashing and disinfection of heavily contaminated hands—effective or ineffective? J Hosp Infect 1992;21(1):61–71.

    CAS  PubMed  Google Scholar 

  17. 17

    Larson E, Silberger M, Jakob K . et al. Assessment of alternative hand hygiene regimens to improve skin health among neonatal intensive care unit nurses. Heart Lung 2000;29(2):136–142.

    CAS  PubMed  Google Scholar 

  18. 18

    Pittet D . Compliance with hand disinfection and its impact on hospital-acquired infections. J Hosp Infect 2001;48(Suppl A):S40–S46.

    PubMed  Google Scholar 

  19. 19

    Pittet D . Improving adherence to hand hygiene practice: a multidisciplinary approach. Emerg Infect Dis 2001;7(2):234–240.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Pittet D . Promotion of hand hygiene: magic, hype, or scientific challenge? Infect Control Hosp Epidemiol 2002;23(3):118–119.

    PubMed  Google Scholar 

  21. 21

    Boyce JM, Kelliher S, Vallande N . Skin irritation and dryness associated with two hand-hygiene regimens: soap-and-water hand washing versus hand antisepsis with an alcoholic hand gel. Infect Control Hosp Epidemiol 2000;21(7):442–448.

    CAS  PubMed  Google Scholar 

  22. 22

    Doebbeling BN, Stanley GL, Sheetz CT et al. Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units. N Engl J Med 1992;327(2):88–93.

    CAS  PubMed  Google Scholar 

  23. 23

    Larson EL, Laughon BE . Comparison of four antiseptic products containing chlorhexidine gluconate. Antimicrob Agents Chemother 1987;31(10):1572–1574.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Larson EL, Eke PI, Wilder MP, Laughon BE . Quantity of soap as a variable in handwashing. Infect Control 1987;8(9):371–375.

    CAS  PubMed  Google Scholar 

  25. 25

    Hirschmann H, Fux L, Podusel J et al. The influence of hand hygiene prior to insertion of peripheral venous catheters on the frequency of complications. J Hosp Infect 2001;49(3):199–203.

    CAS  PubMed  Google Scholar 

  26. 26

    Hugonnet S, Perneger TV, Pittet D . Alcohol-based handrub improves compliance with hand hygiene in intensive care units. Arch Intern Med 2002;162(9):1037–1043.

    PubMed  Google Scholar 

  27. 27

    Meengs MR, Giles BK, Chisholm CD, Cordell WH, Nelson DR . Hand washing frequency in an emergency department. Ann Emerg Med 1994;23(6):1307–1312.

    CAS  PubMed  Google Scholar 

  28. 28

    Voss A, Widmer AF . No time for handwashing! Hand washing versus alcoholic rub: can we afford? 100% complaince? Infect Control Hosp Epidemiol 1997;18(3):205–208.

    CAS  PubMed  Google Scholar 

  29. 29

    Muto CA, Sistrom MG, Farr BM . Hand hygiene rates unaffected by installation of dispensers of a rapidly acting hand antiseptic. Am J Infect Control 2000;28(3):273–276.

    CAS  PubMed  Google Scholar 

  30. 30

    Sharek PJ, Benitz WE, Abel NJ, Freeburn MJ, Mayer ML, Bergman DA . Effect of an evidence-based hand washing policy on hand washing rates and false-positive coagulase negative staphylococcus blood and cerebrospinal fluid culture rates in a level III NICU. J Perinatol 2002;22(2):137–143.

    PubMed  Google Scholar 

  31. 31

    Foca M, Jakob K, Whittier S et al. Endemic Pseudomonas aeruginosa infection in a neonatal intensive care unit. N Engl J Med 2000;343(10):695–700.

    CAS  PubMed  Google Scholar 

  32. 32

    Moolenaar RL, Crutcher JM, San Joaquin VH et al. A prolonged outbreak of Pseudomonas aeruginosa in a neonatal intensive care unit: did staff fingernails play a role in disease transmission? Infect Control Hosp Epidemiol 2000;21(2):80–85.

    CAS  PubMed  Google Scholar 

  33. 33

    McNeil SA, Foster CL, Hedderwick SA, Kauffman CA . Effect of hand cleansing with antimicrobial soap or alcohol-based gel on microbial colonization of artificial fingernails worn by health care workers. Clin Infect Dis 2001;32(3):367–372.

    CAS  PubMed  Google Scholar 

  34. 34

    Pottinger J, Burns S, Manske C . Bacterial carriage by artificial versus natural nails. Am J Infect Control 1989;17(6):340–344.

    CAS  PubMed  Google Scholar 

  35. 35

    Narayanan I, Prakash K, Gujral VV . The value of human milk in the prevention of infection in the high-risk low-birth-weight infant. J Pediatr 1981;99(3):496–498.

    CAS  PubMed  Google Scholar 

  36. 36

    Hylander MA, Strobino DM, Dhanireddy R . Human milk feedings and infection among very low birth weight infants. Pediatrics 1998;102(3):E38.

    CAS  Google Scholar 

  37. 37

    Schanler RJ . The use of human milk for premature infants. Pediatr Clin North Am 2001;48(1):207–219.

    CAS  Google Scholar 

  38. 38

    Ohlsson A, Lacy JB . Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants. Cochrane Database Syst Rev 2001;(2):CD000361.

    Google Scholar 

  39. 39

    Jenson HB, Pollock BH . Meta-analyses of the effectiveness of intravenous immune globulin for prevention and treatment of neonatal sepsis. Pediatrics 1997;99(2):E2.

    CAS  PubMed  Google Scholar 

  40. 40

    Ohlsson A, Lacy JB . Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2001;(2):CD001239.

    Google Scholar 

  41. 41

    American Institute of Architects. Guidelines for Design and Construction of Hospital and Health Care Facilities. Washington, DC: The American Institute of Architects; 2001.

  42. 42

    O'Grady NP, Alexander M, Dellinger EP et al. Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention. MMWR Recomm Rep 2002;51(RR-10):1–29.

    PubMed  Google Scholar 

  43. 43

    Garland JS, Henrickson K, Maki DG . The 2002 Hospital Infection Control Practices Advisory Committee Centers for Disease Control and Prevention guideline for prevention of intravascular device-related infection. Pediatrics 2002;110(5):1009–1013.

    PubMed  Google Scholar 

  44. 44

    Salzman MB, Isenberg HD, Shapiro JF, Lipsitz PJ, Rubin LG . A prospective study of the catheter hub as the portal of entry for microorganisms causing catheter-related sepsis in neonates. J Infect Dis 1993;167(2):487–490.

    CAS  Google Scholar 

  45. 45

    Salzman MB, Rubin LG . Intravenous catheter-related infections. Adv Pediatr Infect Dis 1995;10:337–368.

    CAS  Google Scholar 

  46. 46

    Sitges-Serra A, Hernandez R, Maestro S, Pi-Suner T, Garces JM, Segura M . Prevention of catheter sepsis: the hub. Nutrition 1997;13(4 Suppl):30S–35S.

    CAS  PubMed  Google Scholar 

  47. 47

    Sitges-Serra A, Girvent M . Catheter-related bloodstream infections. World J Surg 1999;23(6):589–595.

    CAS  PubMed  Google Scholar 

  48. 48

    Ng SP, Gomez JM, Lim SH, Ho NK . Reduction of nosocomial infection in a neonatal intensive care unit (NICU). Singapore Med J 1998;39(7):319–323.

    CAS  PubMed  Google Scholar 

  49. 49

    Salzman MB, Isenberg HD, Rubin LG . Use of disinfectants to reduce microbial contamination of hubs of vascular catheters. J Clin Microbiol 1993;31(3):475–479.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Segura M, Alia C, Oms L, Sancho JJ, Torres-Rodriguez JM, Sitges-Serra A . In vitro bacteriological study of a new hub model for intravascular catheters and infusion equipment. J Clin Microbiol 1989;27(12):2656–2659.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Segura M, Alia C, Valverde J, Franch G, Torres Rodriguez JM, Sitges-Serra A . Assessment of a new hub design and the semiquantitative catheter culture method using an in vivo experimental model of catheter sepsis. J Clin Microbiol 1990;28(11):2551–2554.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52

    Segura M, Alvarez-Lerma F, Tellado JM et al. A clinical trial on the prevention of catheter-related sepsis using a new hub model. Ann Surg 1996;223(4):363–369.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Garland JS, Alex CP, Mueller CD et al. A randomized trial comparing povidone-iodine to a chlorhexidine gluconate-impregnated dressing for prevention of central venous catheter infections in neonates. Pediatrics 2001;107(6):1431–1436.

    CAS  PubMed  Google Scholar 

  54. 54

    Maki DG, Ringer M, Alvarado CJ . Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991;338(8763):339–343.

    CAS  PubMed  Google Scholar 

  55. 55

    Raad II, Hohn DC, Gilbreath BJ et al. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994;15(4 Part 1):231–238.

    CAS  PubMed  Google Scholar 

  56. 56

    Mermel LA, McCormick RD, Springman SR, Maki DG . The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan–Ganz catheters: a prospective study utilizing molecular subtyping. Am J Med 1991;91(3B):197S–205S.

    CAS  PubMed  Google Scholar 

  57. 57

    Lopez Sastre JB, Coto CD, Fernandez CB . “Neonatal sepsis of nosocomial origin: an epidemiological study from the "Grupo de Hospitales Castrillo”. J Perinat Med 2002;30(2):149–157.

    CAS  PubMed  Google Scholar 

  58. 58

    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(1):34–39.

    PubMed  Google Scholar 

  59. 59

    Nagata E, Brito AS, Matsuo T . Nosocomial infections in a neonatal intensive care unit: incidence and risk factors. Am J Infect Control 2002;30(1):26–31.

    PubMed  Google Scholar 

  60. 60

    Chathas MK, Paton JB, Fisher DE . Percutaneous central venous catheterization. Three years' experience in a neonatal intensive care unit. Am J Dis Child 1990;144(11):1246–1250.

    CAS  Google Scholar 

  61. 61

    Kennedy KA, Tyson JE, Chamnanvanikij S . Early versus delayed initiation of progressive enteral feedings for parenterally fed low birth weight or preterm infants. Cochrane Database Syst Rev 2000;(2):CD001970.

    Google Scholar 

  62. 62

    Kennedy KA, Tyson JE, Chamnanvanakij S . Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed low-birth-weight infants. Cochrane Database Syst Rev 2000;(2):CD001241.

    Google Scholar 

  63. 63

    Craft AP, Finer NN, Barrington KJ . Vancomycin for prophylaxis against sepsis in preterm neonates. Cochrane Database Syst Rev 2000;(2):CD001971.

    Google Scholar 

  64. 64

    DeLisle S, Perl TM . Vancomycin-resistant enterococci: a road map on how to prevent the emergence and transmission of antimicrobial resistance. Chest 2003;123(5 Suppl):504S–518S.

    CAS  PubMed  Google Scholar 

  65. 65

    Lai KK, Fontecchio SA, Kelley AL, Baker S, Melvin ZS . The changing epidemiology of vancomycin-resistant enterococci. Infect Control Hosp Epidemiol 2003;24(4):264–268.

    PubMed  Google Scholar 

  66. 66

    Pierce CM, Wade A, Mok Q . Heparin-bonded central venous lines reduce thrombotic and infective complications in critically ill children. Intensive Care Med 2000;26(7):967–972.

    CAS  PubMed  Google Scholar 

  67. 67

    Jansen B, Ruiten D, Pulverer G . In-vitro activity of a catheter loaded with silver and teicoplanin to prevent bacterial and fungal colonization. J Hosp Infect 1995;31(3):238–241.

    CAS  PubMed  Google Scholar 

  68. 68

    McCarthy A, Rao JS, Byrne M, Breatnach F, O'Meara CA . Central venous catheter infections treated with teicoplanin. Eur J Haematol Suppl 1998;62:15–17.

    CAS  PubMed  Google Scholar 

  69. 69

    Jansen B, Jansen S, Peters G, Pulverer G . In-vitro efficacy of a central venous catheter (‘Hydrocath’) loaded with teicoplanin to prevent bacterial colonization. J Hosp Infect 1992;22(2):93–107.

    CAS  PubMed  Google Scholar 

  70. 70

    Kamal GD, Pfaller MA, Rempe LE, Jebson PJ . Reduced intravascular catheter infection by antibiotic bonding. A prospective, randomized, controlled trial. JAMA 1991;265(18):2364–2368.

    CAS  PubMed  Google Scholar 

  71. 71

    Jansen B, Kristinsson KG, Jansen S, Peters G, Pulverer G . In-vitro efficacy of a central venous catheter complexed with iodine to prevent bacterial colonization. J Antimicrob Chemother 1992;30(2):135–139.

    CAS  PubMed  Google Scholar 

  72. 72

    Kristinsson KG, Jansen B, Treitz U, Schumacher-Perdreau F, Peters G, Pulverer G . Antimicrobial activity of polymers coated with iodine-complexed polyvinylpyrrolidone. J Biomater Appl 1991;5(3):173–184.

    CAS  PubMed  Google Scholar 

  73. 73

    Pai MP, Pendland SL, Danziger LH . Antimicrobial-coated/bonded and -impregnated intravascular catheters. Ann Pharmacother 2001;35(10):1255–1263.

    CAS  PubMed  Google Scholar 

  74. 74

    Veenstra DL, Saint S, Saha S, Lumley T, Sullivan SD . Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis. JAMA 1999;281(3):261–267.

    CAS  PubMed  Google Scholar 

  75. 75

    Elliott T . Intravascular catheter-related sepsis—novel methods of prevention. Intensive Care Med 2000;26(Suppl 1):S45–S50.

    PubMed  Google Scholar 

  76. 76

    Hanley EM, Veeder A, Smith T, Drusano G, Currie E, Venezia RA . Evaluation of an antiseptic triple-lumen catheter in an intensive care unit. Crit Care Med 2000;28(2):366–370.

    CAS  PubMed  Google Scholar 

  77. 77

    Darouiche RO, Raad II, Heard SO et al. A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group. N Engl J Med 1999;340(1):1–8.

    CAS  PubMed  Google Scholar 

  78. 78

    Benjamin Jr. DK, Miller W, Garges H et al. Bacteremia, central catheters, and neonates: when to pull the line. Pediatrics 2001;107(6):1272–1276.

    PubMed  Google Scholar 

  79. 79

    Nazemi KJ, Buescher ES, Kelly Jr. RE, Karlowicz MG . Central venous catheter removal versus in situ treatment in neonates with enterobacteriaceae bacteremia. Pediatrics 2003;111(3):e269–e274.

    PubMed  Google Scholar 

  80. 80

    Karlowicz MG, Furigay PJ, Croitoru DP, Buescher ES . Central venous catheter removal versus in situ treatment in neonates with coagulase-negative staphylococcal bacteremia. Pediatr Infect Dis J 2002;21(1):22–27.

    PubMed  Google Scholar 

  81. 81

    Chapman RL, Faix RG . Persistent bacteremia and outcome in late onset infection among infants in a neonatal intensive care unit. Pediatr Infect Dis J 2003;22(1):17–21.

    PubMed  Google Scholar 

  82. 82

    Bloom BT, Craddock A, Delmore PM et al. Reducing acquired infections in the NICU: observing and implementing meaningful differences in process between high and low acquired infection rate centers. J Perinatol 2003;23(6):489–492.

    PubMed  Google Scholar 

  83. 83

    Long MN, Wickstrom G, Grimes A, Benton CF, Belcher B, Stamm AM . Prospective, randomized study of ventilator-associated pneumonia in patients with one versus three ventilator circuit changes per week. Infect Control Hosp Epidemiol 1996;17(1):14–19.

    CAS  PubMed  Google Scholar 

  84. 84

    Cordero L, Sananes M, Ayers LW . Comparison of a closed (Trach Care MAC) with an open endotracheal suction system in small premature infants. J Perinatol 2000;20(3):151–156.

    CAS  PubMed  Google Scholar 

  85. 85

    Deppe SA, Kelly JW, Thoi LL et al. Incidence of colonization, nosocomial pneumonia, and mortality in critically ill patients using a Trach Care closed-suction system versus an open-suction system: prospective, randomized study. Crit Care Med 1990;18(12):1389–1393.

    CAS  PubMed  Google Scholar 

  86. 86

    Tan SG, Lim SH, Malathi I . Does routine gowning reduce nosocomial infection and mortality rates in a neonatal nursery? A Singapore experience. Int J Nurs Pract 1995;1(1):52–58.

    CAS  PubMed  Google Scholar 

  87. 87

    Donowitz LG . Failure of the overgown to prevent nosocomial infection in a pediatric intensive care unit. Pediatrics 1986;77(1):35–38.

    CAS  PubMed  Google Scholar 

  88. 88

    Pelke S, Ching D, Easa D, Melish ME . Gowning does not affect colonization or infection rates in a neonatal intensive care unit. Arch Pediatr Adolesc Med 1994;148(10):1016–1020.

    CAS  PubMed  Google Scholar 

  89. 89

    Krediet TG, Beurskens FJ, van Dijk H, Gerards LJ, Fleer A . Antibody responses and opsonic activity in sera of preterm neonates with coagulase-negative staphylococcal septicemia and the effect of the administration of fresh frozen plasma. Pediatr Res 1998;43(5):645–651.

    CAS  PubMed  Google Scholar 

  90. 90

    Burgner D . Fresh frozen plasma and neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 1994;71(3):F233.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91

    Acunas BA, Peakman M, Liossis G et al. Effect of fresh frozen plasma and gammaglobulin on humoral immunity in neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 1994;70(3):F182–F187.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92

    Campbell JR, Zaccaria E, Baker CJ . Systemic candidiasis in extremely low birth weight infants receiving topical petrolatum ointment for skin care: a case-control study. Pediatrics 2000;105(5):1041–1045.

    CAS  PubMed  Google Scholar 

  93. 93

    Lund C, Kuller J, Lane A, Lott JW, Raines DA . Neonatal skin care: the scientific basis for practice. Neonatal Netw 1999;18(4):15–27.

    CAS  PubMed  Google Scholar 

  94. 94

    Lund CH, Osborne JW, Kuller J, Lane AT, Lott JW, Raines DA . Neonatal skin care: clinical outcomes of the AWHONN/NANN evidence-based clinical practice guideline. Association of Women's Health, Obstetric and Neonatal Nurses and the National Association of Neonatal Nurses. J Obstet Gynecol Neonatal Nurs 2001;30(1):41–51.

    CAS  PubMed  Google Scholar 

  95. 95

    Lund CH, Kuller J, Lane AT, Lott JW, Raines DA, Thomas KK . Neonatal skin care: evaluation of the AWHONN/NANN research-based practice project on knowledge and skin care practices. Association of Women's Health, Obstetric and Neonatal Nurses/National Association of Neonatal Nurses. J Obstet Gynecol Neonatal Nurs 2001;30(1):30–40.

    CAS  PubMed  Google Scholar 

  96. 96

    Janota J, Stranak Z, Belohlavkova S . Interleukin-6, procalcitonin, C-reactive protein and the immature to total neutrophil ratio (I/T) in the diagnosis of early-onset sepsis in low birth weight neonates. Ceska Gynekol 2000;65(Suppl 1):29–33.

    PubMed  Google Scholar 

  97. 97

    Magudumana MO, Ballot DE, Cooper PA et al. Serial interleukin 6 measurements in the early diagnosis of neonatal sepsis. J Trop Pediatr 2000;46(5):267–271.

    CAS  PubMed  Google Scholar 

  98. 98

    Mehr S, Doyle L . Interleukin-6 concentrations in neonatal sepsis. Lancet 1999;353(9166):1798–1799.

    CAS  PubMed  Google Scholar 

  99. 99

    Yilmaz E, Gurgoze MK, Ilhan N, Dogan Y, Aydinoglu H . Interleukin-8 levels in children with bacterial, tuberculous and aseptic meningitis. Indian J Pediatr 2002;69(3):219–221.

    PubMed  Google Scholar 

  100. 100

    Sikora JP, Chlebna-Sokol D, Krzyzanska-Oberbek A . Proinflammatory cytokines (IL-6, IL-8), cytokine inhibitors (IL-6sR, sTNFRII) and anti-inflammatory cytokines (IL-10, IL-13) in the pathogenesis of sepsis in newborns and infants. Arch Immunol Ther Exp (Warsz) 2001;49(5):399–404.

    CAS  Google Scholar 

  101. 101

    Schollin J . Interleukin-8 in neonatal sepsis. Acta Paediatr 2001;90(9):961–962.

    CAS  PubMed  Google Scholar 

  102. 102

    Mehr SS, Doyle LW, Rice GE, Vervaart P, Henschke P . Interleukin-6 and interleukin-8 in newborn bacterial infection. Am J Perinatol 2001;18(6):313–324.

    CAS  PubMed  Google Scholar 

  103. 103

    Martin H, Olander B, Norman M . Reactive hyperemia and interleukin 6, interleukin 8, and tumor necrosis factor-alpha in the diagnosis of early-onset neonatal sepsis. Pediatrics 2001;108(4):E61.

    CAS  PubMed  Google Scholar 

  104. 104

    Franz AR, Steinbach G, Kron M, Pohlandt F . Interleukin-8: a valuable tool to restrict antibiotic therapy in newborn infants. Acta Paediatr 2001;90(9):1025–1032.

    CAS  PubMed  Google Scholar 

  105. 105

    Franz AR, Steinbach G, Kron M, Pohlandt F . Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Pediatrics 1999;104(3 Part 1):447–453.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106

    Franz AR, Kron M, Pohlandt F, Steinbach G . Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants. Pediatr Infect Dis J 1999;18(8):666–671.

    CAS  Google Scholar 

  107. 107

    Enguix A, Rey C, Concha A, Medina A, Coto D, Dieguez MA . Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children. Intensive Care Med 2001;27(1):211–215.

    CAS  PubMed  Google Scholar 

  108. 108

    Ronnestad A, Abrahamsen TG, Gaustad P, Finne PH . C-reactive protein (CRP) response patterns in neonatal septicaemia. APMIS 1999;107(6):593–600.

    CAS  PubMed  Google Scholar 

  109. 109

    Benitz WE, Han MY, Madan A, Ramachandra P . Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 1998;102(4):E41.

    CAS  PubMed  Google Scholar 

  110. 110

    Pourcyrous M, Bada HS, Korones SB, Baselski V, Wong SP . Significance of serial C-reactive protein responses in neonatal infection and other disorders. Pediatrics 1993;92(3):431–435.

    CAS  PubMed  Google Scholar 

  111. 111

    Ang AT, Ho NK, Chia SE . The usefulness of CRP and I/T ratio in early diagnosis of infections in Asian newborns. J Singapore Paediatr Soc 1990;32(3–4):159–163.

    CAS  PubMed  Google Scholar 

  112. 112

    Seibert K, Yu VY, Doery JC, Embury D . The value of C-reactive protein measurement in the diagnosis of neonatal infection. J Paediatr Child Health 1990;26(5):267–270.

    CAS  PubMed  Google Scholar 

  113. 113

    de Man P, Verhoeven BA, Verbrugh HA, Vos MC, van den Anker JN . An antibiotic policy to prevent emergence of resistant bacilli. Lancet 2000;355(9208):973–978.

    CAS  PubMed  Google Scholar 

  114. 114

    Sinkowitz RL, Keyserling H, Walker TJ, Holland J, Jarvis WR . Epidemiology of vancomycin usage at a children's hospital, 1993 through 1995. Pediatr Infect Dis J 1997;16(5):485–489.

    CAS  Google Scholar 

  115. 115

    Stoll BJ, Hansen N, Fanaroff AA et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002;110(2 Part 1):285–291.

    PubMed  Google Scholar 

  116. 116

    Karlowicz MG, Buescher ES, Surka AE . Fulminant late-onset sepsis in a neonatal intensive care unit, 1988-1997, and the impact of avoiding empiric vancomycin therapy. Pediatrics 2000;106(6):1387–1390.

    CAS  PubMed  Google Scholar 

  117. 117

    Benjamin Jr. DK, Ross K, McKinney Jr. RE, Benjamin DK, Auten R, Fisher RG . When to suspect fungal infection in neonates: A clinical comparison of Candida albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal bacteremia. Pediatrics 2000;106(4):712–718.

    Google Scholar 

  118. 118

    Garcia-Prats JA, Cooper TR, Schneider VF, Stager CE, Hansen TN . Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system. Pediatrics 2000;105(3 Part 1):523–527.

    CAS  PubMed  Google Scholar 

  119. 119

    Kumar Y, Qunibi M, Neal TJ, Yoxall CW . Time to positivity of neonatal blood cultures. Arch Dis Child Fetal Neonatal Ed 2001;85(3):F182–F186.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120

    Kaiser JR, Cassat JE, Lewno MJ . Should antibiotics be discontinued at 48 hours for negative late-onset sepsis evaluations in the neonatal intensive care unit? J Perinatol 2002;22(6):445–447.

    PubMed  Google Scholar 

  121. 121

    Kurlat I, Stoll BJ, McGowan Jr. JE . Time to positivity for detection of bacteremia in neonates. J Clin Microbiol 1989;27(5):1068–1071.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. 122

    Pauli Jr. I, Shekhawat P, Kehl S, Sasidharan P . Early detection of bacteremia in the neonatal intensive care unit using the new BACTEC system. J Perinatol 1999;19(2):127–131.

    PubMed  Google Scholar 

  123. 123

    Pichichero ME, Todd JK . Detection of neonatal bacteremia. J Pediatr 1979;94(6):958–960.

    CAS  Google Scholar 

  124. 124

    Hertz D, Fuller D, Davis T, Papile L, Stevenson D, Lemons J . Comparison of DNA probe technology and automated continuous-monitoring blood culture systems in the detection of neonatal bacteremia. J Perinatol 1999;19(4):290–293.

    CAS  PubMed  Google Scholar 

  125. 125

    Rowley AH, Wald ER . Incubation period necessary to detect bacteremia in neonates. Pediatr Infect Dis 1986;5(5):590–591.

    CAS  Google Scholar 

  126. 126

    Kicklighter SD . Antifungal agents and fungal prophylaxis in the neonate. NeoReviews 2002;3(12):249e–2255.

    Google Scholar 

  127. 127

    Hudome SM, Fisher MC . Nosocomial infections in the neonatal intensive care unit. Curr Opin Infect Dis 2001;14(3):303–307.

    CAS  PubMed  Google Scholar 

  128. 128

    Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Donowitz LG . Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med 2001;345(23):1660–1666.

    CAS  PubMed  Google Scholar 

  129. 129

    Kicklighter SD, Springer SC, Cox T, Hulsey TC, Turner RB . Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant. Pediatrics 2001;107(2):293–298.

    CAS  PubMed  Google Scholar 

  130. 130

    Hurley R, Winner HI . Experimental moniliasis in the mouse. J Pathol Bacteriol 1963;86:75–81.

    CAS  PubMed  Google Scholar 

  131. 131

    Hurley R . The pathogenicity of Candida stellatoidea. J Pathol Bacteriol 1965;90(1):351–354.

    CAS  PubMed  Google Scholar 

  132. 132

    Beno DW, Mathews HL . Quantitative measurement of lymphocyte mediated growth inhibition of Candida albicans. J Immunol Methods 1993;164(2):155–164.

    CAS  PubMed  Google Scholar 

  133. 133

    Rex JH, Walsh TJ, Anaissie EJ . Fungal infections in iatrogenically compromised hosts. Adv Intern Med 1998;43:321–371.

    CAS  PubMed  Google Scholar 

  134. 134

    Hughes WT . Systemic candidiasis: a study of 109 fatal cases. Pediatr Infect Dis 1982;1(1):11–18.

    CAS  PubMed  Google Scholar 

  135. 135

    Telenti A, Roberts GD . Fungal blood cultures. Eur J Clin Microbiol Infect Dis 1989;8(9):825–831.

    CAS  PubMed  Google Scholar 

  136. 136

    Berenguer J, Buck M, Witebsky F, Stock F, Pizzo PA, Walsh TJ . Lysis–centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn Microbiol Infect Dis 1993;17(2):103–109.

    CAS  Google Scholar 

  137. 137

    Benjamin Jr. DK, Miller WC, Bayliff S, Martel L, Alexander KA, Martin PL . Infections diagnosed in the first year after pediatric stem cell transplantation. Pediatr Infect Dis J 2002;21(3):227–234.

    PubMed  Google Scholar 

  138. 138

    Leibovitz E . Neonatal candidosis: clinical picture, management controversies and consensus, and new therapeutic options. J Antimicrob Chemother 2002;49(Suppl 1):69–73.

    CAS  PubMed  Google Scholar 

  139. 139

    Rex JH, Walsh TJ, Sobel JD et al. Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. Clin Infect Dis 2000;30(4):662–678.

    CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Reese Clark MD.

Additional information

Disclosures: None.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Clark, R., Powers, R., White, R. et al. Prevention and Treatment of Nosocomial Sepsis in the NICU. J Perinatol 24, 446–453 (2004).

Download citation

Further reading