preventing nosocomial bloodstream 2002 (hendra)

8/3/2019 Preventing Nosocomial Bloodstream 2002 (Hendra)

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Semin Neonatol 2002; 7: 325333

doi:10.1053/siny.2002.9125, available online at http://www.idealibrary.com on

Preventing nosocomial bloodstream infection in very

low birth weight infants

William H. Edwards

Department of Pediatrics,

Childrens Hospital at Dartmouth,

One Medical Center Drive, Lebanon,

New Hampshire 03756, USA

Nosocomial sepsis is a frequent complication of caring for very low birth weight

infants and incidence varies substantially among centres. Many cases are preventable.

An organized approach to understanding the epidemiology of nosocomial sepsis within

a unit, and implementing evidence-based practices can successfully reduce the incidence.

Diagnostic accuracy is important to limit excess empiric antibiotic therapy. Instituting a

hand hygiene program of education, monitoring, and consideration of waterless hand

disinfectants to avoid hand transmission of organisms is essential. An emphasis on

early achievement of enteral nutrition, preferably with human milk is important to

reduce unnecessary exposure to central catheters and parenteral nutrition. Use of

maximum sterile barrier precautions by personnel trained and skilled in central catheter

insertion, followed by meticulous care in preventing catheter hub contamination will

reduce the incidence of catheter related sepsis. Ultimately, the culture of the NICU

needs to shift from a focus on early detection of infection to one of prevention.

2002 Elsevier Science Ltd. All rights reserved.

Key words: infant, very low birth

weight; cross infection; sepsis; infant,

premature, diseases, infant, premature;

intensive care, neonatal; total quality

management; quality assurance,

health care

Introduction

Survival for very low birth weight (VLBW) infantshas steadily improved. From 1988 to 1996, theNational Institute of Child Health and HumanDevelopment (NICHD) neonatal network reportedincreased survival from 74% to 84% [1]. Increasedmorbidity has accompanied better survival rates,however. Nosocomial infection is frequent, and isnot only a risk for mortality, but also adds to

length of hospital stay and costs of care [24].Multiple studies have identified risk factors associ-ated with nosocomial bloodstream infections.Incidence of nosocomial sepsis is inversely relatedto birth weight and gestational age, higher inmales, and directly correlates with severity ofillness scores, ventilator days, length of stay, corti-costeroid use, use of central catheters, and

parenteral nutrition, especially intravenous lipids[510].

Comparing incidence rates for nosocomial infec-tions in neonatal intensive care units is mademore difficult by lack of standard definitions. TheCenter for Disease Controls National NosocomialInfections Surveillance (NNIS) system defineslaboratory-confirmed bloodstream infection as therecovery of a recognized pathogen from one ormore blood cultures. Classification of commonskin contaminants (e.g. diptheroids, Bacillus sp.,

Propionibacterium sp., coagulase-negative staphylo-cocci, or micrococci) recovered from culture as abloodstream infection requires symptoms (fever>38C, hypothermia


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infections, although separately designated asmaternally acquired [5,11]. The NICHD neonatalresearch network defines sepsis as positive resultsfrom one or more blood cultures, in the presence ofclinical signs or symptoms suggestive of infection,and antibiotic treatment for 5 or more days. Theyfurther designate sepsis as early onset (positive

culture obtained at


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tract. Infections due to Pseudomonas sp. are rela-tively less common, but may be difficult to controldue to persistence in reservoirs in the environment[21,22]. Fungal organisms are commensal organ-isms that colonize the skin and gastrointestinaltract. Infections are related to disease severity andpresence of invasive therapies, and prolonged

exposure to antibiotics [23,24]. The incidence offungal sepsis in VLBW infants is 23% [3,13], buthas been reported to be as high as 20% for infantsweighing less than 1000 grams at birth [25]. It isdifficult to dissociate the morbidity caused bynosocomial infection from the underlying diseaseseverity associated with problems of extreme pre-maturity. However, mortality rates associated withgram-negative and fungal sepsis are much higherthan for gram-positive organisms. Case fatalityrate in the NICHD neonatal research network for

infections with all gram-positive organisms was10.1%, compared to 39.6% for all gram-negativesand 28.1% for fungi. Mortality associated withPseudomonas sepsis was 61.8% [3]. A clear under-standing of the profile of organisms causing noso-comial sepsis in a neonatal intensive care nursery isvital to prioritizing strategies for prevention.

Diagnosis

Making an accurate diagnosis of sepsis in VLBWinfants is sometimes difficult. Some episodes ofsepsis have low quantitative counts of organisms inthe blood, although the actual incidence of lowcolony count sepsis by organism type is not known[26]. The relationship between culture volume anddetection of sepsis in adults is clearly established[27]. Concern about excessive blood losses fromtesting and technical difficulties obtaining sufficientblood volume from arterial or venous puncturesoften result in small volumes of blood for culture.

A reasonable recommendation is to obtain a mini-mum of 1 ml of blood for culture [28]. Positivecultures obtained from indwelling arterial orvenous catheters may reflect colonization of thecatheter or the hub rather than bloodstream infec-tion. To improve diagnostic accuracy, it is oftenrecommended to obtain two culturesone fromthe indwelling catheter and a second from directarterial or venous puncture. Concordance betweenthe two cultures, either positive or negative,increases confidence in diagnosing or ruling outsepsis. Discordant results from two cultures are

most often interpreted as the positive culture beinga contaminant [29]. An alternative interpretationcould be that in low colony count sepsis theadditional sample increases the chances fordetecting a true infection.

Limiting unnecessary empiric antibiotic therapyshould be a major motivation to accurately diag-

nose nosocomial sepsis. Frequent suspicion of sep-sis along with the often subtle presenting clinicalsigns result in liberal use of broad-spectrum anti-biotics. Antibiotic use then increases the risk ofopportunistic infections in individual patients andthe risk of developing antibiotic resistance inorganisms over time [23,24,30,31]. Widespreadvancomycin use to empirically cover coagulase-negative staphylococci may contribute to infec-tions from more virulent gram-negative organismsand the emergence of vancomycin resistant entero-

cocci [1820,32]. Improvements in blood culturesystems with automated detection has reduced thetime to positive results [33]. Empiric antibiotictherapy pending culture results should be no morethan 48 h when such a system is in place.

Unit culture

One of the most important strategies for prevent-ing nosocomial sepsis, at the same time most

difficult to study and quantify, is the role of unitculture. During a quality improvement project toreduce nosocomial sepsis rates in VLBW infants,site visits were made to two NICUs with thelowest incidence of nosocomial sepsis in theVermont Oxford Network [12]. Two attributes ofthese benchmark units were apparent: the staffs ofthe units were both aware and proud of their lownosocomial sepsis rate, and they believed noso-comial infection was preventable. When an infantdeveloped an infection, it was considered a break-

down in care. Two conceptual models for a unitsbeliefs about nosocomial sepsis are proposed inTable 1, a model of entitlement, and one ofprevention. In the entitlement model, there is afatalistic belief that nosocomial sepsis is inevitabledue to factors beyond the control of the careteam. VLBW infants have inherent deficiencies inimmunity, and risks associated with necessary andlife-saving care, such as invasive lines, parenteralnutrition and ventilator support are unavoidable.The focus of the care team is on detecting earlysigns of infection and starting treatment early. The

Preventing nosocomial bloodstream infection in very low birth weight infants 327


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team may take pride in its ability to detect subtlepresenting clinical signs, and sepsis work-ups andempiric courses of antibiotics pending cultureresults are frequent. Ultimately, no connection ismade between a lapse in ideal care, for example

leading to colonization and infection of a centralline, and the event of sepsis. Lack of ownership isfurther hampered by the interval between the carefailure and the downstream event, making it diffi-cult to even suspect such a connection. In contrastto the entitlement model, in the prevention modelthe inherent risk due to impaired immunity is alsoacknowledged, but the focus is on developing carepractices that minimize the risk. An episode ofnosocomial sepsis prompts a review to determinewhether any events or breaks in ideal care practices

might have contributed. Most important, beliefthat nosocomial sepsis is preventable leads tomotivation to improve. Because nosocomial infec-tions are multifactorial in origin (Fig. 1), i t i sparticularly important for all team members tounderstand the units goal of nosocomial infectionprevention, and their role in adhering to ideal carepractices and encouraging creativity in proposingpotential improvements in care.

Hand hygiene

Endemic strains of bacteria or fungi may persist inNICUs over months to even decades, and aretransmitted to new patients by hand transmission[3436]. The importance of hand transmissionin nosocomial infections has been emphasized inmultiple recent reviews, and many guidelines exist[3740]. Evidence-based reviews of hand hygienehave been recently published [41,42]. Health careproviders generally acknowledge the importanceof handwashing, but overestimate their owncompliance [43]. If it is clearly important, but care

providers fail to do it, is there any hope that handhygiene can be improved? Several studies holdpromise. Better accessibility of sinks is associatedwith improved handwashing, while installation ofautomated sinks have little lasting benefit [44,45].

Waterless hand rub sanitizers have been shown tobe effective in decontaminating hands and aregenerally well tolerated [46]. Introducing theseproducts has led to improved hand decontamina-tion in some, but not all trials [4750]. Use ofwaterless hand rubs may reduce time required fortraditional handwashing, making compliance morelikely and cost-effective [51]. A variety of educa-tional strategies have improved hand disinfection,but without ongoing monitoring, the effect istransient [45,52]. An innovative approach has been

taken of educating patients about the importance ofhandwashing, and asking that they remind theircaregivers to wash. For adult medical and surgicalpatients, compliance with handwashing was in-creased by 34% and 50% in two studies [53,54]. Allpatients asked nurses to wash hands, but only 35%asked physicians [54]. The possibility of includingparents as partners ensuring compliance with handdecontamination guidelines in NICUs should bestudied.

Protecting the hands against irritation and break-down is important. A small study showed that

nurses with hand irritation had greater numbers ofcolonizing species [55]. Recently, artificial nailshave been implicated as potential risk factors fortransmission of gram-negative bacteria, particularlyPseudomonas aeruginosa, and should be prohibitedfrom use in the NICU [21,56,57].

Nutrition

Besides the widely held belief that better nu-trition enhances immune function and helps resist

Table 1. Two conceptual models for nosocomial sepsis in VLBW infants

Entitlement Prevention

Causality Unavoidable inherent risk from

poor immune function and necessary

invasive care

Preventable in most

instances

Focus of care team Early detection PreventionWhy did it happen? Chance or unavoidable Breakdown in ideal careResponsibility Babys vulnerability Care teamMotivation for improvement Fatalistic, inevitable Challenge to continually

improve

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infection, nutrition care practices may relate tonosocomial infection risk in other ways. Noso-comial sepsis incidence correlates with parenteralnutrition, especially intravenous lipids, as well aswith the central lines often placed primarily forgiving parenteral nutrition [3,4,69]. Although it isreasonable to assume that limiting exposure to

central lines and parenteral nutrition by earlierestablishment of enteral nutrition might reduce theincidence of nosocomial sepsis, there are no specifictrials with that primary hypothesis. There is evi-dence that early initiation of enteral feedings whilean umbilical artery catheter is in situ is safe, andresults in fewer days on parenteral nutrition [58]. Ina systematic review of minimal enteral nutrition,or trophic feedings, defined as providing =5 days, infants in the studygroups reached full enteral feeds sooner, with fewer

days total days feedings were held. The incidenceof necrotizing enterocolitis was not significantlydifferent among groups. Nosocomial sepsis was nota reported outcome [59].

The possibility that human milk feedings reducerisk of nosocomial sepsis has been suggested inseveral small studies and is reviewed more exten-sively in this issue by Hanson [6062]. Feedingstudies with pre-term mothers breast milk com-pared to premature infant formula are difficult toconduct due to the lack of random allocation, lackof ability to blind care providers, and need to

supplement breast milk with formula when supplyis inadequate. el-Mohandes and co-workers consid-ered infants to be human milk-fed if they receivedonly human milk as an enteral nutrient for >=1week, or if human milk accounted for at least 40%of their total enteral caloric intake. By that defini-tion, 59 were fed human milk and 114 formula. Theodds ratio for sepsis in the human milk-fed groupcompared with formula was 0.38 (95% confidenceinterval 0.150.95, P=0.04). In the Schanler study,the human milk group was defined as receiving an

average of>=

50 ml/kg/day of human milk duringhospitalization. There were 62 infants in the human

milk group and 46 in the formula group. Theincidence of sepsis was not significantly different(31% vs 48%, P=0.07), but the combined incidenceof sepsis and/or necrotizing enterocolitis was less inthe human milk group compared to the formulagroup (31% vs 54%, P


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colonization leading to infection has been describedin several adult and neonatal studies [7072].Saltzman and co-workers studied 113 catheters in88 neonates. In 10 of 28 episodes of catheter-related sepsis, the organism isolated from bloodwas isolated from a culture of the catheter hubprior to the onset of clinical sepsis, and in 5

additional episodes, simultaneously. The commonsense preventive measure of limiting the number ofconnecting hubs is suggested by a prospectiverandomized clinical trial where episodes ofcatheter-related sepsis were more common withtriple lumen than with single lumen catheters [73].Carefully devised techniques of maintaining hubsterility during line changes and active decontami-nation of the catheter hub may be effective inlimiting hub colonization [15,74]. Saltzman andco-workers developed an in vitro model to study

hub disinfection and emphasized the importance ofmechanical friction, which was 99% effective in hubdecontamination. The use of 70% alcohol com-pleted the disinfection [75]. There is promise thatwith better understanding of the epidemiologyof catheter colonization, new designs may beeffective in reducing catheter-related sepsis [76,77].Antibiotic impregnated catheters have strong evi-dence for efficacy in preventing catheter-relatedsepsis in adults, and research in developing similarmaterials for use in neonates should be encouraged[42].

Since by far the most common organismassociated with neonatal catheter-related sepsis iscoagulase-negative staphylococcus, a number ofclinical trials have been conducted using vancomy-cin prophylaxis, and the practice has been thesubject of a critical review [78]. Although effectivein reducing the incidence of coagulase-negativestaphylococcal sepsis, the lack of proven benefitfor other important clinical outcomes of mortalityand length of stay along with concern for thedevelopment of vancomycin resistance in other

organisms are reasons for caution in recommendingwidespread use of this strategy [20,78].

Skin care

The skin of the premature infant is exceedinglyfragile, particularly in the first weeks after birth.Multiple care practices are associated with skinbreakdown, including epidermal stripping fromtapes and adhesives, abrasions from rough ma-

terials and skin punctures for blood sampling.Nopper and Lane in a study designed to measurethe effects of an emollient ointment on insensiblewater loss, found an unexpected reduction in theincidence of nosocomial sepsis in the group treatedwith twice a day application of the ointment fortwo weeks [79]. A randomized clinical trial of

infants weighing 5011000 grams at birth of simi-lar design failed to confirm a benefit of reducednosocomial sepsis. The group receiving prophy-lactic application of emollient ointment actuallyhad a higher incidence of nosocomial infection [80].Additional reports have associated ointments withinfection. Campbell and co-workers in a case-control study demonstrated a potential relationshipbetween the topical application of petrolatum oint-ment and systemic candidiasis in infants weighing


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preventing nosocomial bloodstream 2002 (hendra)

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