central venous catheters ( cvcs ) are widely used in neonatal intensive care units ( nicus ) .
the most common types of cvcs used in nicus are umbilical venous catheters ( uvc ) , peripherally inserted central catheters ( picc ) , and tunneled cvc ( e.g. , hickman and broviac)1 ) .
uvcs , which are cvcs inserted through the umbilical vein , have been frequently used in nicus for many years1 ) .
complications of uvc use are thrombosis , hemorrhage , arrhythmias , effusions , and portal hypertension . due to heavy bacterial growth around the umbilicus and the risk of infection ,
piccs are used in very - low - birth - weight infants ( vlbw ) when an intolerance for adequate oral feeding beyond 7 days of life is expected or when total parenteral nutrition is required for more than 1 week2 ) .
the peripheral veins used for cannulation include the greater and lesser saphenous veins of the lower extremities and the basilic or cephalic veins of the upper extremities , which are preferred over femoral sites .
piccs may lead to obstruction , rupture , vessel perforation , extravasation , thrombosis , and infection . to decrease the risk of these complications , correct
picc tip placement in non - central sites in children , including the subclavian or brachiocephalic vein , has been shown to significantly increase the rate of complications3 ) .
tip placement in the right atrium increases the risk of arrhythmia and pericardial tamponade1,4 ) .
the most appropriate location for the tip of piccs is the lower one - third of the superior vena cava if the picc is placed in an upper extremity and the inferior vena cava if the picc is placed in a lower extremity4 ) .
they are usually considered when the cvc is needed for more than 6 weeks5 ) .
vlbw infants are vulnerable to infections because of their immature immune systems , frequent contact with hospital personnel , and invasive procedures .
the rates of catheter - related bloodstream infection ( crbsi ) range from 6.4 to 8.3 episodes per 1,000 patientdays in the nicu6 ) , with the smallest and most immature infants being at the greatest risk .
crbsis contribute to increased morbidity and mortality , prolonged hospitalization , and the need for additional therapies .
therefore , nicu staffs have attempted to reduce infection rates by using insertion and maintenance protocols to prevent crbsi .
this review will define catheter - related infections and discuss their pathophysiology , risk factors , and microbiology as well as strategies to minimize crbsi .
the range of healthcare associated infections with cvc includes not only laboratory - confirmed bloodstream infection ( bsi ) , but also clinical sepsis7 - 9 ) .
the definitions of laboratory - confirmed bsi is isolation of recognized pathogens from blood culture that were not related to infection at another site , with clini cal characteristics of sepsis .
the definition of catheter colonization is absence of infection signs and significant growth of micro - organisms from the catheter tip , subcutaneous segment of the catheter , or catheter hub . to identify the infection or colonization , distal portion of catheter
is rolled four times over the surface of a sheep - blood agar plate and the number of microorganisms microorganisms ( > 15 colony - forming units ) is determined after 48 hours of incubation . like this
, semiquantitative culture technique identifies only microorganisms from the external surface of the catheter , while quantitative cultures allow the identification of micro - organisms from both the internal and the external surfaces of the catheters .
crbsi is defined as a laboratory - confirmed bsi with either a positive catheter tip culture or a positive blood culture drawn from the cvc . however , central line - associated bloodstream infection ( clabsi ) is that bacteremia occurs with a central line in place or within 48 hours of a central line removal with clinical symptoms of sepsis and no other apparent source of infection , with or without positive culture through the catheter .
the definition of clinical sepsis requires the following conditions : clinical symptoms or signs for sepsis , blood culture not done or no organism or antigen detected in blood , and no apparent infection at another site .
cvcs are prone to bacterial infections , particularly staphylococcus aureus and coagulase - negative staphylococci . it is known that fibrinogen and fibronectin are dominant plasma mediators in staphylococcal adherence and deposited on inserted catheters10 ) . also , staphylococci are colonized to the cvc surface by the formation of a multilayered biofilm ( slime ) , conferring some protection against antibiotics11 ) .
healthcare associated infections with cvc occur by four distinct pathways in infection process , including external and internal catheter surface colonization pathways , intrinsic contamination , and hematogenous seeding .
external surface pathway infection may start with the colonization of the skin insertion site by micro - organisms of the skin flora that may move by capillary action through the transcutaneous part of the dermal tunnel surrounding the catheter .
internal surface pathway infection occurs by colonization of the hub and intraluminal surface of the catheter12 ) .
contamination of the fluids or drugs intravenously administered ( so - called " intrinsic contamination " ) constitutes another process responsible for crbsis , sometimes resulting in outbreaks .
, serratia marcescens , malasezia furfur , or candida parapsilosis are identified in some circumstances13 ) .
finally , hematogenous seeding of the catheter during bsi of any origin represents a third pathway of crbsis14 ) .
zingg et al.9 ) presented that the median time to a infection for piccs and umbilical catheters was 7 ( interquartile range , 5 to 10 ) and 7 ( interquartile range , 5 to 8) days , respectively .
hoang et al.15 ) reported a median time of 9 days for piccs of the upper extremities , although the median time was longer ( 15 days ) for piccs of the lower extremities .
the national institute of child health and human development neonatal research network showed that the risk of late - onset sepsis increased as the duration of cvc and parenteral nutrition increased , and infants who developed sepsis had higher mean indwelling times than infants without sepsis .
the risk of late - onset sepsis increased significantly for catheters in place for 22 or more days16 ) .
some authors reported that low birth weight is the most important factor for the occurrence of clabsi / crbsi .
de brito et al.17 ) showed that neonates weighing less than 750 g revealed the highest crbsi incidence rate ( 3.3/1,000 days cvc ) . in the national healthcare safety network survey18 ) , the rate of crbsis was 4.4 to 6.4 per 1,000 catheter days among neonates weighing less than 1,000 g. anticoagulants are used widely to prevent catheter thrombosis . because thrombi and fibrin deposits on catheters might serve as a nidus for microbial colonization of cvc
it is known that surface heparinization appears to have a great impact on bacterial colonization and can be a significant approach to the prevention of catheter - associated bacteremia or fungemia19 ) .
venous access can be difficult in vlbw infants , and a femoral vein can be the alternative site available for cannulation after failure to insert cvcs in all other peripheral veins .
although the hospital infection control practices advisory committee , center for disease control and prevention in united states recommends that femoral catheters should be avoided when possible , because they are associated with a higher risk for deep vein thrombosis and more likely to become infected20 ) , there were reports that there were no differences among sites of catheter placement15,21 ) .
most microorganisms implicated in crbsis are gram - positive cocci , which are responsible for at least two - thirds of infections2 ) .
de brito et al.17 ) reported that coagulase - negative staphylococci ( cons ) were the most common microorganism implicated in laboratory - confirmed bsi ( 39.7% ) and clabsi / crbsi ( 42.9% and 60.0% , respectively ) , and s. aureus was the second leading cause of bsi .
, acinetobacter baumannii , escherichia coli , pseudomonas aeruginosa ) are responsible for a higher proportion of crbsis in icu patients than in non - icu patients .
these infections result from colonization of invasive pressure monitoring systems , complicated remote infections , or high levels of orotracheal colonization22 ) .
. have emerged as important pathogens in crbsis and account for a high proportion of the dramatic increase in the rate of candidemia over recent decades .
they represented more than 30% of pathogens reported from 1992 to 1998 in 204 mixed icus participating in the u.s .
national nosocomial infection surveillance system23 ) , confirming that intravascular devices constitute the leading cause of nosocomial candidemia . however , the incidence of each pathogen isolated from catheters differed among nicus2,9,15 ) .
bacteremic infants have fewer infection - related complications when the cvc is removed promptly24 ) . a single blood culture positive for s. aureus or a gram - negative rod warrants central line removal in a neonate . for neonates with 1 positive culture for cons , clinicians may attempt medical management without central catheter removal , but documentation of subsequent negative blood cultures is crucial . once a neonate has had 3 positive blood cultures for cons , the central catheter should be removed .
there is evidence that fluconazole provides antifungal prophylaxis for infants < 1,000 g and/or < 27 weeks ' gestation25 ) . to have the greatest effect and target the highest risk period , antifungal prophylaxis
should be started within the first 2 days of life and continue until central or peripheral iv access is no longer needed .
strategies to reduce crbsi include : 1 ) precaution during line insertion ; 2 ) management of cvc and cvc - connection ; 3 ) reduction of the duration of time that the cvc is used ; 4 ) vancomycin prophylaxis for cvcs ; 5 ) removal of the cvc when there is a positive culture .
maximal universial precautions ( e.g. , caps , masks , sterile gowns , and sterile gloves ) during catheter acquire reduction of crbsi incidence , compared with standard precautions .
taylor et al.26 ) reported that crbsi in vlbw infants requiring long term central venous access was reduced by nearly half after the institution of a dedicated picc team in the nicu .
schulman et al.27 ) reported that statewide application of standardized , evidence - based central - line insertion and maintenance bundles substantially reduced nicu clabsis .
bundles are defined as a limited number of specific practices essential for effective and safe patient care that , when implemented together , result in additional improvements in patient outcomes .
insertion bundles include establishment of a cvc insertion kit , hand hygiene with appropriate antiseptic agents before the procedure , maximal universal precautions , and patient disinfection with appropriate antiseptics ( e.g. , 2% chlorhexidine , 70% alcohol ) .
proper maintenance bundles of the cvc should include hand hygiene with antiseptics before dressing catheter site , the establishment of a sterile field , limiting frequency of blood collection through the catheter , rubbing the hub vigorously with disinfectants ( e.g. , 2% chlorhexidine , 70% alcohol ) at the time of hub entry or disconnection , daily change of administration sets ( e.g. , intravenous tubing set)28 ) , avoiding the use of multilumen catheters , integrity of the dressing , evaluation of catheter site for signs of infection , and re - evaluation of catheter necessity and prompt removal of catheter that you no longer need .
a 10% povidone - iodine solution is usually used as a disinfectant for whole - skin surfaces of all nursery patients .
the use of chg for the insertion and maintenance of cvcs is recommended for adult and pediatric populations over povidone iodine , although its use is still controversial in neonates . the u.s .
federal drug administration has not approved chg for cutaneous use in infants less than 2 months of age . nevertheless , off - label use of chg in nicus is common : more than 60% of u.s .
the concentration of chg used for neonates is lower than that used for adults ( 0.5% vs. 2.0% ) , although its effectiveness is possibly reduced30 ) .
garland et al.31 ) reported severe contact dermatitis with the use of a chg impregnated patch that was placed over catheter sites after insertion .
most episodes occurred in neonates who were < 1 week old and < 28 weeks ' gestation at birth .
garland et al.25 ) suggested that occlusion , pressure created by the dressing , chg , or a combination of all 3 factors was responsible for severe contact dermatitis of the dressing site . in a randomized clinical trial , prophylactic use of a heparinized saline containing vancomycin 25
ug / ml ( antibiotic lock technique ) markedly reduced the incidence of crbsi in vlbw infants with piccs and did not promote no vancomycin - resistant enterococci or cons32 ) .
however , several issues still need to be resolved before the routine use of antibiotic lock to prevent crbsi .
they include ideal dwell times and drug concentrations , progressive reduction of antibiotic activity , compatibility between antibiotics and heparin , antimicrobial resistance and risk of systemic toxicity , and universal application of antibiotic lock technique awaits validation by larger clinical trials33 ) .
since cvc have been used as a routine tool for administration of the hyperosmolar fluid or medications to vlbw infants , catheter - related infection remains a leading cause of healthcare associated infections in nicus .
the incidence of each pathogen isolated from catheter was individualized on nicus , even though two - thirds of micro - organisms implicated in infections arise from gram - positive cocci , including cons and staphylococcus aureus .
because crbsi / clabsi contribute to increased morbidity , mortality , and prolonged hospitalization , nicu staffs have tried to reduce these infection rates with the control of risk factors and strict adherence of protocols for the insertion and maintenance of cvc .
strategies to reduce crbsi include : 1 ) precaution during line insertion and maintenance of cvc and tubing set ; 2 ) reduction of the duration of time that cvc is used ; 3 ) vancomycin prophylaxis for cvcs ; 4 ) prompt removal of the cvc when there is a positive culture and you no longer need , and re - evaluation of catheter necessity .
 central venous catheters ( cvcs ) are regularly used in intensive care units , and catheter - related bloodstream infection ( crbsi ) remains a leading cause of healthcare - associated infections , particularly in preterm infants . 
 increased survival rate of extremely - low - birth - weight infants can be partly attributed to routine practice of cvc placement . 
 the most common types of cvcs used in neonatal intensive care units ( nicus ) include umbilical venous catheters , peripherally inserted central catheters , and tunneled catheters . 
 crbsi is defined as a laboratory - confirmed bloodstream infection ( bsi ) with either a positive catheter tip culture or a positive blood culture drawn from the cvc . 
 bsis most frequently result from pathogens such as gram - positive cocci , coagulase - negative staphylococci , and sometimes gram - negative organisms . 
 crbsis are usually associated with several risk factors , including prolonged catheter placement , femoral access , low birth weight , and young gestational age . 
 most nicus have a strategy for catheter insertion and maintenance designed to decrease crbsis . 
 specific interventions slightly differ between nicus , particularly with regard to the types of disinfectants used for hand hygiene and appropriate skin care for the infant . in conclusion , 
 infection rates can be reduced by the application of strict protocols for the placement and maintenance of cvcs and the education of nicu physicians and nurses . 
Introduction
Definitions
Pathophysiology
Risk factors
Microbiology
Management
Prevention
Conclusion