Article

infectious diseases

Nosocomial Infections in the Neonatal Intensive Care Unit

Richard A. Polin, MD,* Lisa Saiman, MD, MPH

Objectives

After completing this article, readers should be able to:

1. List the primary pathogens involved in late-onset infections. 2. List the major risk factors for nosocomial sepsis. 3. Describe practices that can reduce the risk of nosocomial infections.

Introduction
Improvements in antenatal management and neonatal intensive care over the past 10 to 15 years have changed the prognosis for preterm infants. More than 85% of infants born at 25 weeks gestation now survive their preterm birth. This has resulted in a dramatic change in the populations of infants occupying neonatal intensive care beds. The average length of stay for a term or near-term infant who has surgical or respiratory problems is about 15 days; the length of stay for preterm infants born at 26 weeks gestation is more than 2 months. The duration of hospitalization is inversely related to gestational age. The population of extremely low-birthweight (ELBW) infants who remain hospitalized for extended periods of time (and who undergo numerous invasive procedures) is most susceptible to nosocomial infections. Nosocomial infections are dened as those that occur beyond 48 hours after birth and are caused by pathogens that are not maternally derived. Such infections are 100 times more common than early-onset bacterial infections, which are caused by pathogens acquired in utero or perinatally. Recent data from the National Institute of Child Health and Human Development-sponsored Neonatal Network indicated that 29% of infants born at 25 to 28 weeks gestation and 46% of infants born at less than 25 weeks gestation experience a serious nosocomial infection during hospitalization in the NICU. The morbidity and mortality from nosocomial infections is enormous. In the United States, more than 2,000,000 nosocomial infections (in infants and adults) occur each year, Abbreviations and 50% to 60% are caused by resistant organisms. It has been estimated that 9,600 to 20,000 patients die each year in CONS: coagulase-negative staphylococci the United States from catheter-related bloodstream infecELBW: extremely low-birthweight tions. Nosocomial infections increase the costs of neonatal ESBL: extended-spectrum beta-lactamase-producing intensive care, prolong hospitalization by several weeks, and G-CSF: granulocyte colony-stimulating factor are responsible for almost 50% of the deaths that occur GM-CSF: granulocyte-macrophage colony-stimulating beyond 2 weeks of age. Although the epidemiology of factor neonatal nosocomial infections is complex, both simple and HICPAC: Healthcare Infection Control Practices theoretical strategies can reduce the frequency of hospitalAdvisory Committee acquired infections. This article discusses the epidemiology IVIG: intravenous immune globulin and prevention of nosocomial infections in the neonatal MRSA: methicillin-resistant Staphylococcus aureus intensive care unit (NICU). MSSA: methicillin-susceptible Staphylococcus aureus
NICU: RSV: VRE: VREF: neonatal intensive care unit respiratory syncytial virus vancomycin-resistant enterococci vancomycin-resistant Enterobacter faecium

Epidemiology and Microbiology

Over the past 50 years, the epidemiology of pathogens responsible for nosocomial infections in neonates has changed dramatically. During the 1950s, Staphylococcus

*Professor of Pediatrics, Division of Neonatology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University; Director, Division of Neonatology, Childrens Hospital of New York Presbyterian, New York, NY. Associate Professor of Clinical Pediatrics, Division of Infectious Disease, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY. NeoReviews Vol.4 No.3 March 2003 e81

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aureus phage type 80/81 was the Table 1. most common nosocomial pathogen in hospitalized infants. During the 1960s, gram-negative bacilli, including Pseudomonas aeruginosa, Site of Infection Common Pathogens Less Common Pathogens Klebsiella sp, and Escherichia coli, became the most common pathoBloodstream/sepsis CONS Enterococci gens. By the 1970s, coagulaseStaphylococcus aureus Klebsiella sp Pseudomonas aeruginosa Serratia marcescens negative staphylococci (CONS) Candida sp Enterobacter sp (predominantly S epidermidis) and Malassezia sp S aureus, including methicillinPneumonia CONS Enterococci resistant S aureus (MRSA), became S aureus Klebsiella sp the predominant causes of hospitalP aeruginosa S marcescens Respiratory syncytial virus Inuenza acquired infections in the NICU. Skin/soft tissue/surgical site CONS Enterococci Today, gram-positive cocci conS aureus S marcescens tinue to cause the largest proAspergillus sp portion of infections, and many, Gastrointestinal tract Rotavirus Anaerobic bacteria including MRSA, CONS, and Coronavirus Conjunctivitis/Ocular CONS S marcescens vancomycin-resistant enterococci P aeruginosa (VRE), are multidrug-resistant. Urinary tract Gram-negative bacilli Candida sp Gram-negative bacilli are responsiEnterococci ble for 20% to 30% of cases of lateEndocarditis CONS Candida sp onset sepsis and 30% of nosocomial S aureus Central nervous system CONS S marcescens pneumonias (Table 1). Many gramS aureus Enterobacter sp negative pathogens are also Candida sp multidrug-resistant, including orOsteoarthritis S aureus Gram-negative bacilli ganisms that express extendedGroup B streptococci Candida sp spectrum beta-lactamases such as K CONS coagulase-negative staphylococci, S aureus include methicillin-resistant S aureus, Enterococcal pneumoniae, K oxytoca, and other sp include vancomycin-resistant enterococci enterobacteriaceae such as E coli. Such enzymes can degrade thirdthe NICU. The burden of infections from these microgeneration cephalosporins, and organisms expressing organisms in affected infants is enormous. Approxithese beta-lactamases may be treated successfully only mately 40% of all infections are caused by CONS, and with carbapenem antibiotics such as imipenem and nearly 5% of NICU patients develop bacteremia with meropenem. Candida sp, particularly C albicans and C CONS. Overall, these pathogens are responsible for 40% parapsilosis, have become increasingly common and to 50% of bloodstream infections; 29% of eye, ear, nose, cause about 10% of late-onset infections. Finally, viral and throat infections; 19% of skin and soft-tissue infecpathogens also can cause infections in NICU patients, tions; 16% of pneumonias; and 10% of infections of the and outbreaks of respiratory syncytial virus (RSV) and gastrointestinal tract. The precise incidence of CONS rotavirus infections (in parallel with community outinfections is difcult to determine because it often is breaks) have been well described. Because every unit has difcult to distinguish a true infection with CONS from its own, unique endemic ora, active surveillance for culture contamination if only one blood culture is nosocomial infections is critical to guide empiric antibiobtained. otic therapy and implement effective preventive strateCONS also can cause meningitis, ventriculoperitoneal gies. shunt infections, and right-sided endocarditis associated Bacterial Pathogens with the use of central venous catheters or umbilical Coagulase-negative Staphylococci venous catheters. Infections due to CONS are late-onset Since the late 1970s and early 1980s, CONS, particularly infections; bloodstream infections occur most commonly S epidermidis, have been recognized as the most comduring the third week of hospitalization. Fortunately, mon cause of hospital-acquired infections in infants in CONS infections generally are more indolent than infece82 NeoReviews Vol.4 No.3 March 2003

Nosocomial Infections and Infectious Pathogens in Patients in the Neonatal Intensive Care Unit

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tions caused by other pathogens, but occasionally CONS infections can follow a virulent course, particularly in young, ELBW (1,000 g) infants, and rarely they can cause death. The increase in infections due to CONS is presumed to be due to the improved survival and prolonged hospitalization of ELBW infants and the increasing prevalence of specic risk factors. Risk factors for CONS infections include use of central venous catheters, intravenous lipids, parenteral nutrition, mechanical ventilation, and increased severity of illness. The pathogenesis of CONS is related to patterns of colonization; CONS colonize the skin of preterm infants, contaminate the outside of central venous catheters or catheter hubs, track down the catheters, and cause bloodstream infections. Most CONS infections are believed to be endemic, but there are numerous examples of outbreaks. Strains may persist in an intensive care unit for years. Molecular typing by pulsed-eld gel electrophoresis and other genetic typing technologies is extremely helpful and can identify outbreak strains; phenotyping is unreliable because speciation by biochemical proles is inexact and CONS usually are multidrug-resistant.

Enterococci
Enterococci are an occasional cause of infections in the NICU. Overall, 6% of late-onset sepsis cases, 5% of pneumonias, and 9% of surgical site infections are caused by enterococcal species. The Pediatric Prevention Network point-prevalence survey from 1999 reported that 10.3% of bloodstream infections and 16.7% of urinary tract infections were attributed to enterococci. Risk factors for colonization of the gastrointestinal tract and subsequent infection include increased length of hospitalization, use of indwelling catheters, and prolonged use of antibiotics. Outbreaks of vancomycin-resistant E faecium (VREF) have been described. Extensive environmental contamination has been noted, and outbreaks have been terminated successfully by improved cleaning, restricted use of vancomycin, cohorting of infected/colonized infants, and the use of contact precautions. Among the risk factors for VREF are prolonged treatment with antimicrobial agents and low birthweight.

Gram-negative Pathogens
PSEUDOMONAS AERUGINOSA P aeruginosa is a well known cause of sepsis, pneumonia, conjunctivitis, and endophthalmitis and is associated with high mortality rates. Potential reservoirs for P aeruginosa in the NICU include resuscitation equipment, humidiers, incubators, formulas, breast pumps, sinks and sink drains, tap water, infants who have prolonged lengths of stay, and the hands of healthcare workers. Among the risk factors for P aeruginosa infection are feeding intolerance, prolonged need for parenteral hyperalimentation, and prolonged treatment with antibiotics. KLEBSIELLA SP Klebsiella sp, particularly K pneumoniae and K oxytoca, are well-established pathogens in NICU patients that cause sepsis, urinary tract infections, and pneumonia. During the 1970s, the most common cause of outbreaks in the NICU was Klebsiella sp, and most were kanamycin-resistant. More recently, extended-spectrum beta-lactamase-producing (ESBL) Klebsiella sp have been identied that are resistant to third-generation cephalosporins. The plasmid containing the ESBL gene can be transmitted to other Enterobacteriaceae sp in vivo. ENTEROBACTER SP Enterobacter sp, such as E cloacae, E agglomerans, and E sakazakii, are less common causes of hospital-acquired infections in NICUs. Enterobacter sp are multidrugNeoReviews Vol.4 No.3 March 2003 e83

Staphylococcus aureus
S aureus is a common pathogen in the NICU and may be virulent. S aureus causes bloodstream infections and sepsis, skin/soft-tissue/wound infections, osteoarthritis (which can be multifocal), and less commonly, central nervous system infections such as meningitis and ventriculitis. Similarly to CONS, the pathogenesis of S aureus is related to patterns of colonization. It can colonize the skin, nares, nasopharynx, gastrointestinal tract, respiratory tract, or eyes. Approximately 7% to 9% of cases of late-onset sepsis, 17% of pneumonias, and 22% of surgical site infections in patients in the NICU are caused by S aureus. Risk factors for methicillin-susceptible S aureus (MSSA) infection/ colonization include prolonged duration of hospitalization and low birthweight. Most MRSA infections appear to be associated with outbreaks. Healthcare workers frequently are implicated in transmission; MRSA colonize the anterior nares and spread from patient to patient by transient hand carriage. MRSA can become endemic and may colonize as many as 36% of infants in an NICU. Risk factors for MRSA acquisition are increased length of hospitalization, antibiotic exposure, and instrumentation (eg, indwelling catheters). MRSA does not appear to be more virulent than MSSA, but healthcare costs associated with MRSA are generally higher.

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resistant pathogens and can cause sepsis and meningitis in preterm infants. Infections with these pathogens are associated with high mortality rates. Several outbreaks have been linked to intrinsically contaminated dextrose for intravenous infusion and powdered infant formula.

the source of nosocomial viral infections. Detection of viral pathogens requires a high index of suspicion because symptoms of viral illnesses in preterm infants may be nonspecic (eg, apnea, temperature instability). Appropriate diagnostic studies must be ordered.

Fungal Pathogens
CANDIDA SP For more than 2 decades it has been recognized that preterm infants are at increased risk for infections caused by Candida sp, particularly C albicans and C parapsilosis. Other Candida sp, such as C tropicalis, C lusitaniae, and C glabrata, are less common causes of late-onset sepsis. Resistance to uconazole and amphotericin can occur in Candida sp, and testing for susceptibility should be considered if there is a poor clinical response. Candida sp cause candidemia, particularly catheter-related, bloodstream infection, and less commonly, urinary tract infections, endocarditis, osteomyelitis, and meningitis. The crude mortality rate after infection with Candida sp ranges from 23% to 50%. Risk factors for invasive disease caused by fungal pathogens include prematurity, central venous catheters, histamine2 blockers, antibiotics, parenteral nutrition, intravenous lipids, intubation, prolonged length of hospitalization, and colonization with Candida sp, particularly in the respiratory or gastrointestinal tracts. (See also Kicklighter SD. Antifungal agents and fungal prophylaxis in the neonate. NeoReviews. 2002;3:e249-e255.) MALASSEZIA SP AND TRICHOSPORON SP Malassezia sp, particularly M furfur and M pachydermatis, are well described, less common causes of late-onset infections. The most important risk factor is the use of intravenous lipids because M furfur has the critical growth requirement of exogenous fatty acids C12 to C24. Malassezia sp fungemia generally resolves with central catheter removal; patients do not appear to require systemic antifungal agents.

Bloodstream and Catheter-related Bloodstream Infections

Bloodstream infections represent the most common nosocomial infection of patients in the NICU, and many such infections are catheter-related. ELBW infants exhibit the highest rate of these infections, but bloodstream infections remain the most common infection, even among infants whose birthweights are 2,500 g or greater. Late-onset sepsis is an important determinant of morbidity and mortality; the length of hospitalization increases in infants treated for sepsis. The overall risk of dying of late-onset sepsis is 17%; rates are higher for gram-negative pathogens such as P aeruginosa (40%) and fungi (15% to 50%) and lower for CONS (10%). As even smaller preterm infants survive, the mortality rate due to respiratory causes among infants whose gestational age is 23 to 27 weeks has decreased, but the mortality rate from sepsis increased from 14% in 1983 through 1990 to 44% in 1992 through 1996.

Respiratory Tract Infections

Pneumonia is the second most common nosocomial infection in patients in the NICU and causes about 15% of hospital-acquired infections. The rate of ventilatorassociated pneumonia varies by center, with a median of 3.3 episodes of pneumonia per 1,000 ventilator-days. Although both gram-negative and -positive pathogens cause pneumonia, mortality from the former is much higher. Accurate diagnosis of nosocomial pneumonia can be very difcult in preterm infants because radiographic changes may be due to atelectasis or noninfectious diseases such as bronchopulmonary dysplasia rather than infection, and infants rarely undergo invasive diagnostic procedures such as bronchoscopy.

Viruses
Hospital-acquired viral infections in NICU patients parallel community illnesses. As many as 30% of infections of the gastrointestinal tract and 5% of eye, ear, nose, and throat infections are caused by viral illnesses. Outbreaks caused by respiratory viruses such as RSV and inuenza have been described, as have outbreaks caused by rotavirus. Preterm infants may be asymptomatic and may shed viruses for prolonged periods, thus contaminating the environment and facilitating patient-to-patient spread via the hands of staff. Ill healthcare workers also may be
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Strategies for Prevention of Nosocomial Sepsis

Reducing the incidence of nosocomial sepsis requires a multifaceted approach. Prevention of preterm birth is potentially the most effective strategy to decrease the risk of nosocomial sepsis by reducing the size of the most susceptible population in the NICU. A review of that topic is beyond the scope of this paper (see Guinn D, Gibbs R. Infection-related preterm birth: a review of the evidence. NeoReviews. 2002;3:e86-e96), but it is worth

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noting that the rate of prematurity has signicantly increased in the United States over the past 20 years. There are, however, a number of simple care practices that can reduce the probability of an infant developing a hospital-acquired infection. These include elimination of overcrowding and understafng, careful preparation and storage of infant formulas, decreasing the number of heel sticks and attempts at venipuncture, using single-dose administration of medications such as albumin, avoiding drugs associated with an increased risk of nosocomial infection (histamine2 blockers and dexamethasone), sterilization of resuscitation bags and masks, and use of sterile suctioning techniques. Because many episodes of bacteremia are associated with indwelling lines or mechanical ventilation, common sense dictates avoiding their use or minimizing the number of catheter or ventilator days. Ventilator days can be minimized by using interventions that prevent or lessen the severity of respiratory distress syndrome (eg, antenatal steroids and surfactant), permit rapid weaning (eg, permissive hypercapnia, closure of a patent ductus arteriosus), or use noninvasive forms of respiratory support such as continuous positive airway pressure. Care practices that are likely to reduce the incidence of catheter-related infections include: early institution of enteral feedings, use of human milk feedings, discontinuation of parenteral alimentation (especially intravenous lipids) a few days short of full feedings, impeccable central venous catheter care (sterile insertion techniques by skilled personnel and dressing changes with careful disinfection of the insertion site and care of the hub), limitation of open catheter circuits and heparin ushes, careful preparation of intravenous uids and blood products, and routine change of administration sets every 72 hours (or within 24 hours if lipids are used). Recently suggested novel preventive technologies that have been examined in adults include use of silver sulfadiazineimpregnated catheters and cuffs, heparin-bonded catheters, and antibiotic-coated (eg, rifampin-minocycline) and -impregnated catheters. The latest Healthcare Infection Control Practices Advisory Committee (HICPAC) guidelines (2002) recommend use of chlorhexidine for cutaneous antisepsis and anti-infective-impregnated catheters if institutional rates of infection are greater than 3.3 bloodstream infections per 1,000 catheter days despite full adherence to maximal barrier precautions, especially for high-risk patients. Those guidelines have not been adapted for the neonatal population. Furthermore, antiseptic- or antibiotic-impregnated catheters are unavailable for the NICU population.

Handwashing/Degerming
Handwashing and degerming remain the simplest and most effective methods of preventing transmission of infectious agents from clinicians to infants and infants to infants. Six of seven hospital-based studies (including two in NICUs) demonstrated that improved hand hygiene techniques signicantly reduced infection rates. The fourth edition of the Guidelines for Perinatal Care recommends the following practices:

Personnel should remove rings, watches, and bracelets before entering nursery or obstetric areas. Fingernails should be trimmed short, and no articial ngernails or nail polish should be permitted. A 10-second wash is recommended before and after handling each infant.

Three types of skin ora colonize the hands of nursery personnel: resident ora survive and multiply on the skin, transient ora represent recently acquired supercial contamination and may include pathogens acquired from one patient and potentially transferable to another, and infectious ora (eg, S aureus) are capable of causing localized infections in healthcare workers or infants. Handwashing with soap and water is the most effective method of removing soil or proteinaceous material and also may decrease the number of transient ora (because they reside on the skin surface). However, handwashing with soap and water also carries the risk of dispersing bacterial colonies. Even brief skin-to-skin contact can transmit several logs of bacteria. Degerming (using an alcohol-based hand rub with emollient) currently is recommended before and after all patient contacts. It is effective at reducing the number of bacterial, fungal, and viral pathogens. A number of alcohol-containing products are available, but recent data suggest variations in effectiveness. Skin emollients decrease the dispersal of bacteria, but may reduce the effectiveness of chlorhexidine-containing soaps. Soaps and detergents (particularly those that are anionic and cationic), paper towels, and gloves can damage the skin, and damaged skin harbors more potential pathogens. In addition, frequent handwashing (even with soap and water) may affect skin health adversely by raising the pH. Routine gowning in the nursery has not been shown to be an effective strategy, but should be used by healthcare workers coming in contact with infants who are colonized with pathogenic or resistant microorganisms to avoid contaminating the clothing of healthcare workers. Gloves have been advocated as a method of reducing infections, but they may worsen skin condition and promote bacterial growth. Gloves should
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be worn when caring for infants on droplet or contact precautions or when touching blood, body uids, respiratory tract secretions, mucous membranes, or objects (including equipment) contaminated by these secretions. Needless to say, compliance with handwashing is poor. In a recent interventional study to evaluate the impact of an alcohol-based gel in improving hand hygiene compliance, Harbarth and associates demonstrated that the use of an alcohol-based gel improved compliance, but even with an active educational program, compliance never exceeded 50%. Doctors and nurses remain the least compliant groups. The skin of preterm newborns is thinner, more permeable, and more easily injured with minor trauma compared with term infants. This has led some investigators to recommend application of topical emollients to the smallest infants. Two small, randomized trials suggested that topical emollient therapy might reduce the incidence of bloodstream infections, but the risk of nosocomial infection was not decreased in a recently completed large, randomized clinical trial of infants weighing 500 to 750 g.

added to intravenous solutions. No vancomycin-resistant bacteria were detected in surveillance cultures, but concern about the development of vancomycin resistance remains. This is particularly true in an era when VRE are increasingly prevalent. Furthermore, vancomycin resistance recently has been detected in strains of S aureus. There also has been interest in the use of antifungal agents to prevent infections with Candida sp. The use of topical nystatin has not reduced the incidence of fungal infections. In a recently published randomized clinical trial, the use of prophylactic uconazole resulted in a reduction in colonization and invasive fungal infections. Although uconazole resistance was not detected in this study, resistance to this agent is well described among several Candida sp. A multicenter study is being planned.

Immunoprophylaxis
Reduced transplacental transfer of immunoglobulins and decreased endogenous synthesis of immunoglobulin G predispose preterm infants to nosocomial infections. This physiologic hypogammaglobulinemia provides a rationale for prophylactic administration of intravenous immune globulin (IVIG). Ohlsson and Lacy from the Cochrane Neonatal Group recently reported a metaanalysis of 19 randomized trials of prophylactic immune globulin in very low-birthweight infants. When all studies were combined, there was a signicant (3%) reduction in the incidence of sepsis, but there was no reduction in mortality. Therefore, the use of IVIG is of marginal importance and because of cost considerations should not be used. The recombinant forms of some hematopoietic cytokines have been cloned and puried and have been under clinical investigation for their possible role in modulating the host defense system to prevent neonatal sepsis. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have the ability to increase the number of circulating neutrophils and to augment the cidal activity of neutrophils and macrophages against infectious organisms. Data for the efcacy of G-CSF are limited. A small study (n28) demonstrated reduced infection incidence in babies who had neutropenia born to women who had pregnancy-induced hypertension. In a large randomized clinical trial using GM-CSF (n264), Cairo did not achieve a signicant reduction in the incidence of nosocomial sepsis. However, in a smaller study by Carr (n75), the incidence of bloodstream infection was reduced from 46% to 31% with prophylactic GM-CSF.

Skin Antisepsis
Skin antisepsis at catheter insertion sites and sites of venipuncture is essential. Eight randomized, prospective trials compared 10% povidine-iodine with chlorhexidinecontaining antiseptic for prevention of bloodstream infections involving central venous catheters and arterial catheters. Seven of the trials found lower rates of catheter colonization in the chlorhexidine group, and three of ve trials showed a signicant reduction in central venous catheter-related bloodstream infections. Only a single study (comparing 0.5% chlorhexidine with povidoneiodine) was conducted in a NICU, but the study was not sufciently large to assess differences in bloodstream infection rates. In a recently published randomized trial in neonates, the use of a chlorhexidine patch reduced catheter tip colonization, but not bloodstream infections. Infants assigned to the chlorhexidine patch group had an increased risk of contact dermatitis. At present, skin antisepsis is not recommended for neonates (Infectious Diseases Society of America, HICPAC guidelines).

Antibiotic Prophylaxis
As noted previously, CONS (most frequently S epidermidis) are the most common pathogens responsible for nosocomial sepsis in neonates. Two smaller randomized trials documented a reduction in the number of bloodstream infections when vancomycin (25 mcg/mL) was
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Table 2.

Potential Better Practices for Preventing Nosocomial Infection

Handwashing Meticulous attention to handwashing, with regular monitoring and surveillance of handwashing practice and reporting of compliance. No alteration of hyperalimentation solutions after preparation. Initiation of enteral feedings as early as possible. Reduced exposure to intravenous lipids and hyperalimentation. Promotion of the use of human milk, ensuring proper collection and storage. Initiation of a skin care protocol for all neonates weighing <1,000 g, the goals of which are to promote skin maturation and to prevent skin breakdown. Reduced laboratory testing that requires venipuncture or heelstick. Development of a systematic approach to intravenous therapy that reduces the frequency and number of skin punctures for placement of an intravenous catheter.

Nutrition

Skin Care

with 66 NICUs that did not implement the program, the percentage decrease in nosocomial infection rates and coagulase-negative staphylococcal infections between 1994 and 1996 was greater (P.058 for all nosocomial infections and P.026 for coagulasenegative staphylococcal infections) in the study units. The Vermont Oxford Network now is extending this quality improvement program to other hospitals in its database system.

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 Diagnosis Cairo MS, Agosti J, Ellis R, et al. A ran Establishment of a minimum sample size for a blood culture that is 1 mL per domized, double-blind, placeboaerobic culture bottle. controlled trial of prophylactic recom Preference for two samples of 1 mL each in two aerobic culture bottles. binant human granulocyte Development of a method to distinguish true infection from a contaminated macrophage colony-stimulating factor culture. to reduce nosocomial infections in very low birth weight neonates. J PediRespiratory Care atr. 1999;134:64 70 Minimization of intubation days. Carr R, Modi N, Dore CJ, El-Rifai R, Minimization of the interruption of the ventilator-endotracheal tube circuit. Lindo D. A randomized, controlled trial of prophylactic granulocyteVascular Access macrophage colony-stimulating factor Minimization of the use of central lines, and when used, minimization of the in human newborns less than 32 weeks frequency of daily entries and the duration of use. gestation. Pediatrics. 1999;103: Prospective placement of central lines when intravenous therapy will be of 796 802 long duration. Crunch CJ, Maki DG. The promise of Establishment of sound policies and procedures for line care and access and novel technology for the prevention of regular monitoring of compliance. intravascular device-related bloodstream infection I. Pathogenesis and Unit Culture short-term devices. Clin Infect Dis. Promotion of developmentally supportive care, with an emphasis on minimal 2002;34:1232 handling. Darmstadt GL, Dinulos JC. Neonatal skin Development and maintenance of a culture of cooperation and teamwork that care. Pediatr Clin North Am. 2000; supports and encourages all team members to feel responsible for outcomes. 47:757 Doyle LW, Gultom E, Chuang SL, James M, Davis P, Bowman E. Changing mortality and causes of death in infants 2327 weeks gestaQuality Improvement tional age. J Paediatr Child Health. 1999;35:255259 As noted previously, changing a number of simple care Enterobacter sakazakii infections associated with the use of powpractices can reduce the risk of nosocomial sepsis. dered infant formula Tennessee, 2001. Morb Mortal Wkly Rep MMWR. 2002;51(14):298 300 Horbar and collaborators in the Vermont Oxford Foca M, Jakob K, Whittier S, et al. Endemic Pseudomonas aerugiStudy Group initiated a multidisciplinary collaborative nosa infection in a neonatal intensive care unit. N Engl J Med. quality improvement project to reduce the incidence of 2000;343:695700 nosocomial infections in six intensive care nurseries. InFreeman J, Goldmann DA, Smith NE, Sidebottom DG, Epstein MF, Platt R. Association of intravenous lipid emulsion and terventions fell into six categories (Table 2). Compared
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Suggested Reading

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coagulase-negative staphylococcal bacteremia in neonatal intensive care units. N Engl J Med. 1990;323:301308 Freeman J, Epstein MF, Smith NE, Platt R, Sidebottom DG, Goldmann DA. Extra hospital stay and antibiotic usage with nosocomial coagulase-negative staphylococcal bacteremia in two neonatal intensive care unit populations. Am J Dis Child. 1990;144:324 329 Garland JS, Alex CP, Mueller CD et al. A randomized trial comparing povidine-iodine to a chlorhexidine gluconate impregnated dressing for prevention of central venous catheter infections in infants. Pediatrics. 2001;107:14311436 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(3 Pt 1):357361 Harbarth S, Pittet D, Grady L, et al. Interventional study to evaluate the impact of an alcohol-based hand gel in improving hand hygiene compliance. Pediatr Infect Dis J. 2002;21:489 495 Horbar JD, Rogowski J, Plsek PE, et al. Collaborative quality improvement for neonatal intensive care. Pediatrics. 2001;107: 14 22 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: 1660 1666 Larson E. Skin hygiene and infection prevention: more of the same or different approaches. Clin Infect Dis. 1999;29:127 Mahieu LM, Buitenweg N, Beutels P, De Dooy JJ. Additional hospital stay and charges due to hospital acquired infections in a neonatal intensive care unit. J Hosp Infect. 2001;47:223229 Mahieu LM, De Dooy JJ, Lenaerts AE, Ieven MM, De Muynck AO. Catheter manipulations and the risk of catheter-associated

bloodstream infection in neonatal intensive care patients. J Hosp Infect. 2001;48:20 26 Oelberg DG, Joyner SE, Jiang X, Laborde D, Islam MP, Pickering LK. Detection of pathogen transmission in neonatal nurseries using DNA markers as surrogate indicators. Pediatrics. 2000; 105:311315 Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and or low birth weight infants. The Cochrane Library. 2001;4 Parravicini E. Myeloid hematopoietic growth factors and their role in prevention and/or treatment of neonatal sepsis. Transfusion Med Rev. 2002;16:11 Saiman L, Ludington E, Pfaller M, et al. Risk factors for candidemia in neonatal intensive care unit patients. The National Epidemiology of Mycosis Survey Study Group. Pediatr Infect Dis J. 2000;19:319 324 Sohn AH, Garrett DO, Sinkowitz-Cochran RL, et al. Prevalence of nosocomial infections in neonatal intensive care unit patients: results from the rst national point-prevalence survey. J Pediatr. 2001;139:821 827 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 pt1):285291 The UK Neonatal Stafng Study Group. Patient volume, stafng and workload in relation to risk-adjusted outcomes in a random stratied sample of UK neonatal intensive care units: a prospective evaluation. Lancet. 2002;359:99 Venezia RA, Scarano FJ, Preston KE, et al. Molecular epidemiology of an SHV-5 extended-spectrum beta-lactamase in Enterobacteriaceae isolated from infants in a neonatal intensive care unit. Clin Infect Dis. 1995;21:915923 Wider AF. Replacing hand washing with use of a waterless alcohol hand rub? Clin Infect Dis. 2000;31:136

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NeoReviews Quiz
8. The epidemiology of pathogens responsible for nosocomial sepsis in high-risk neonates has changed over the years. Of the following, the current organism most likely to cause bloodstream infection among highrisk neonates is: A. B. C. D. E.

Candida albicans. Escherichia coli. Pseudomonas aeruginosa. Respiratory syncytial virus. Staphylococcus epidermidis.

9. The risk factors for hospital-acquired infections among infants in the neonatal intensive care unit vary, depending on the involved organism. Of the following, the risk factor most associated with infection by Malassezia furfur is use of: A. B. C. D. E. Antibiotics. Central venous catheter. Endotracheal intubation. Intravenous lipid emulsion. Histamine2 blockers.

10. Reducing the incidence of nosocomial sepsis requires a multifaceted approach. Of the following, the strategy conrmed to be most useful in the prevention of nosocomial sepsis among high-risk neonates is the use of: A. B. C. D. E. Granulocyte colony-stimulating factor. Handwashing. Intravenous immunoglobulin. Skin chlorhexidine antisepsis. Vancomycin in intravenous solutions.

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