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Central venous catheter-related infections: A review
REVIEW ARTICLE
Nutrition Vol. 12, No. 3, 1996
Central Venous Catheter-Related A Review KARIM
A. ADAL, MD, MS,* AND BARRY
Infections:
M. FARR, MD, MSc
From the University of Virginia Health Sciences Center, Charlottesville,
Virginia, USA
Date accepted: 27 October 1995 ABSTRACT
Catheter-associated bloodstream infections remain an important cause of nosocomial infection, with an estimated 50,000100,000 cases occurring each year in the United States. Central venous catheters are believed to be responsible for 90% of such infections. The cumulative risk of acquiring a catheter-related bloodstream infection has ranged between 1 and 10% for central venous catheters in general and 6% for total parenteral nutrition catheters. The skin is the most common source of organisms causing catheter-related infections. Recent prospective studies have shown that the incidence density per catheter day does not increase with duration of catheterization and that routine changes, either over a guidewire or by new site puncture, do not appear to lower the risk of infection. Diagnosis of infection can be difficult in intensive care patients but is usually easier in less ill patients with a central venous catheter. Quantitative or semiquantitative laboratory techniques can be used to confirm the diagnosis in the appropriate clinical setting. A variety of preventive measures have been shown to minimize the risk of development of catheter-related bloodstream infection, including use of maximal aseptic technique for insertion, use of special teams for care of the catheter, limiting manipulation of the catheter, use of povidoneiodine ointment and cotton gauze dressings for recently inserted catheters, a silver-impregnated collagen cuff and antisepticimpregnated catheters. Nutrition 1996; 12:208-213 Key words: central venous catheters, complications,
infection, prevention
INTRODUCTION
Intravenous
catheters
are used in more than 50% of hospital-
ized patients in the United States and are increasingly used in the outpatient setting. There is a wide variety of types of central venous catheters. Pulmonary artery catheters are primarily used for hemodynamic monitoring of critically ill patients. Singleor multilumen nontunneled catheters are frequently placed in hospitalized patients for central access. Tunneled catheters and catheters with subcutaneous infusion ports are frequently used for long-term access in patients with cancer or gastrointestinal disease contraindicating enteral feeding.“Peripherally inserted central catheters have primarily been used in patients requiring infusions for an intermediate duration of several weeks to several months but are now being used with increasing frequency in hospitalized patients. Catheter uses include hemodynamic monitoring; the administration of medications, fluids, blood products or total parenteral nutrition and specialized functions such as hemodialysis and plasmapheresis. Serious mechanical and infectious complications can occur as complications, however, and an estimated 50,000- 100,000 catheter-associated
bloodstream infections occur each year in the United States, ’ associated with a mean excess hospital stay of 7 days.* In this review, we summarize current knowledge of infections associated with these catheters, including a discussion of the pathogenesis, risk factors, diagnosis, therapy and methods of prevention. DEFINITIONS
Significant colonization of the catheter is demonstrated by a positive semiquantitative culture ( 15 or more colony-forming units)334 or quantitative culture (greater than lo2 to 10’ colonyforming units)5 of the catheter tip or subcutaneous segment in the absence of local or systemic symptoms and signs of catheter infection. Exit site infection is present either when frank pus is seen at the site where the catheter penetrates the skin or when there is inflammation (erythema, tenderness and induration) within 2 cm of the skin exit site.6 A semiquantitative or quantitative catheter culture would in most instances be positive with exit site infections, but tunneled catheters are not usually removed
*Current affiliation: The Cleveland Clinic Foundation, Cleveland, OH. Correspondence to: Barry M. Farr, MD, MSc, University of Virginia Health Sciences Center, Box 473, Charlottesville, VA 22908, USA.
Nutrition 12:208-213, 1996 OElsevier Science Inc. 1996 Printed in the USA. All rights reserved.
ELSEVIER
0899-9007/96/$15.00 PII: SO899-9007(96)OC!O41-X
CATHETER-RELATED
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INFECTIONS
in the presence of an exit site infection. Tunnel infection is present when there are signs of inflammation along the tunnel track of a catheter beyond the first 2 cm from the exit site and laboratory values reveal a positive semiquantitative or quantitative catheter culture.6 Catheter-, catheter hub-, or infusate-related bloodstream infection is present when in the absence of other sources of infection, the same organism is cultured from a percutaneous blood culture and, respectively, a semiquantitative (or quantitative) catheter segment culture, a catheter-hub culture or a culture of the infusate.’ Quantitative blood cultures have also been used to define catheter-related bloodstream infection, with a ratio :, 5 in the concentration of microbes in blood aspirated from a central venous catheter to the concentration in blood from a peripheral vein. PATHOGENESIS
A variety of hypotheses have been proposed to explain the events leading to infection of central catheters.7 Bacterial skin colonization at the catheter-skin interface at the time of insertion or afterward with distal spread of the bacteria along the external catheter surface has been the favored theory for shortterm catheters. Other studies have shown that the introduction of bacteria via the catheter hub due to frequent manipulations is another important means of access to the venous circulation*.’ ; this mode is probably more important for long-dwelling catheters.” Contamination of infusate has been rare in recent years?” Contamination of the antiseptic used to prepare the skin before catheter insertion has occurred, particularly with benzalkonium solutions and other quatemary ammonium compounds.12 Seeding of the catheter at the time of bacteremia from a remote source can cause catheter infection.‘.r3.r4 The mechanism may vary depending on the clinical situation, and more than one mechanism may be responsible in the pathogenesis of some cases of catheter infection. Host factors, catheter composition and an interaction between the microorganisms and the catheter can each play an important role in the pathogenesis of catheter-related bloodstream infections.” The dynamic interaction between microorganisms and the catheter involves a series of related steps, beginning with adherence and followed by colonization and dissemination, Host proteins such as fibronectin coat the catheter rapidly once inserted into the patient, providing a substrate for binding of Staphylococcus aureus but not Staphylococcus epidermidis.L6 Slime-producing S. epidermidis expresses a specific polysaccharide capsular adhesion that mediates attachment to the surface of the catheters ‘7~L8 and to heart valves in a rabbit model.” Mutant strains of S. epidermidis that were deficient in slime and capsular polysaccharide adhesin failed to cause endocarditis in rabbits, I9 and rabbits immunized with the adhesin were protected against endocarditis.20 Slime facilitates bacterial persistence on catheters by helping bacteria evade host defenses and also renders the microbes less susceptible to antibiotics.15 MICROBIOLOGY
The skin is the most common source of organisms causing catheter-related infections.7 Coagulase-negative staphylococci are the bacteria most frequently isolated from catheters, but in most cases this colonization does not progress to bacteremia. On the other hand, the isolation of S. aureus from blood cultures is strongly predictive of a catheter-related bacteremia and is associated with a greater incidence of complications such as endocarditis and osteomyelitis. There is a higher incidence of infection with Corynebacterium and Enterococcus species, gram-negative rods and fungi, in infections of tunneled catheters compared with other cathe-
ters, probably reflecting the decreased immune status of the patients with these types of catheters and perhaps the high frequency of antimicrobial exposure which selects for antibiotic-resistant organisms. 21 Candida species and staphylococci are frequent etiologic agents in patients receiving total parenteral nutrition.22.23Malassezia ji&r is mostly seen in neonates receiving intravenous lipid emulsion but can also occur in adults.24 Hematogenous dissemination from another site of infection accounts for greater than 50% of yeast infections, as well as most infections due to enterococcal and gram-negative organisms (e.g., E. coli and Klebsiella species) .5 In the rare infusaterelated infection or infection due to contaminated disinfectant, the organisms are usually gram-negative bacteria that can grow well in such solutions (e.g., Enterobacter, Klebsiella and Pseudomonas species) .25 EPIDEMIOLOGY
AND RISK FACTORS
important risk factor for the development of a catheterrelated infection may be the type of catheter used. The risk of bloodstream infection from a peripheral intravenous catheter is extremely low, less than one bacteremia per 1000 catheters.26-29 By contrast, the risk of acquiring a catheter-related bloodstream infection from nontunneled central venous catheters ranges between 1 and 10% of such catheter insertions, ’and central catheters are believed to account for 90% of catheter-related bloodstream infections.3o Peripherally inserted central catheters have had a low incidence of bacteremia in outpatients3’.32and are much easier to remove than tunneled catheters that require a surgical procedure. Their use in inpatients has not been investigated in randomized trials but may have a low rate of infections as we11?3,” Tunneled catheters and catheters with subcutaneous infusion ports have been associated with an acceptably low incidence of catheter-related bacteremias, but insertion costs are high.3’ Two recent studies have raised questions as to whether tunneling catheters result in lower rates of infection for long-term access. A randomized multicenter trial in France did not find a lower rate for tunneled catheters,35 and a large cohort study of cancer patients at the M.D. Anderson Cancer Center found lower rates with nontunneled subclavian catheters as compared with rates reported for tunneled catheters in cancer patients.31 Several observational studies have reported higher rates of infection with multilumen catheters, and one randomized trial of catheters used for total parenteral nutrition also found a higher rate of infection with multilumen catheters.36 Because study methods stated that two of the lumens of the triple lumen catheters could be used for other infusions and for blood drawing, however, there appeared to be greater chance for manipulation and contamination of the triple lumen catheter than of the single lumen catheter in this trial, and adherence to a protocol for aseptic catheter access was described as “voluntary.” A second randomized trial found no association with multilumen catheters,37 leaving uncertainty as to the importance of multiple lumens. One recent study involving multilumen catheters in intensive care patients reported that only 2% of catheterizations resulted in bloodstream infection, and that there was no association between total parenteral nutrition and infection.4 Catheters used for total parenteral nutrition have been considered to be at higher risk for catheter-related bloodstream infection. Use of a total parenteral nutrition catheter for infusion of other products has been associated with an increased risk of infection?3 However, a decrease in the occurrence of infection from approximately 2530% to 3-5% has been shown to occur with the institution of a dedicated team for the insertion and maintenance care of the alimentation line.’ Three recent studies of the epidemiology of central venous catheter-related bloodstream infection among intensive care patients and cancer patients found no associOne
210
CATHETER-RELATED
ation with parenteral nutrition,4~38~3g suggesting that the team approach to maintenance cam could possibly be valuable for central venous catheters used for other purposes as well. The need to use sterile techniques in handling hyperalimentation fluids and lines is paramount. A needleless intravenous infusion system used for total parenteral nutrition was associated with an increased risk of bloodstream infection in a recent study.4o It is interesting to note that poor glucose control in diabetics has been correlated with a higher incidence of postoperative infections, including bacteremias.4’ This may explain in part the different rates of postoperative infectious complications in a study of surgical patients receiving total parenteral nutrition in which hyperglycemia occurred significantly more in patients randomized to total parenteral nutrition.” Limiting lipid infusions may also decrease the incidence of catheter-related infections?3 More research is needed regarding the effect of metabolic variables on the incidence of catheter infections. Duration of catheterization is an important risk factor for catheter-related bacteremia.g For this mason, several authorities have recommended changing the catheter routinely every few days. Recent prospective studies, however, have shown that the incidence density per catheter day does not increase with increasing duration of catheterization and that routine changes, either over a guidew~e4,3*.44.45 or by new site pun~ture,~~~~do not appear to lower the risk of infection. Regular guidewire exchanges may actually increase the risk of infection.4~38”5 Neutropenia is a significant risk for infections in general, and in one recent study of cancer patients with tunneled central catheters, it was the only independent risk factor for catheter infection.3g Another study found that hematologic neoplasms were significant risk factors for catheter infection,46 but neutropenia was not assessed as an independent variable and is known to occur more frequently with hematologic neoplasms. Male sex was also suggested to be a risk factor in the latter study, but this has not been demonstrated in previous studies and would require confirmation. The use of strict aseptic procedures for the insertion of the catheter has resulted in a lower risk of subsequent catheter infection.47 In two studies, the risk of infection was inversely proportional to the number of previous catheters inserted by the physician.48V4g Subsequent catheter care such as the use of povidoneiodine ointment5’ and gauze dressings” has been associated with a decrease in the risk of catheter-related infection in some studies. Observational studies have generally shown lower rates with subclavian placement than with placement in the internal jugular or femoral vein,‘253 but not all studies have shown high rates with the latter two approaches.48*” Intensive care is associated with an increased number of catheter manipulations for hemodynamic monitoring that in turn is associated with an increased risk of catheter-related bloodstream infections.23 CLINICAL FEATURES AND DIAGNOSIS
diagnosis of catheter-related bloodstream infection can be difficult. Local clinical signs such as tenderness, erythema or pumlence are present in only about 30% of cases involving central catheters.s5 The most common manifestation is fever alone, but hypothermia, rigors, tachypnea, hypotension and/or confusion may also be present. A careful ophthahnoscopic examination must be performed because the appearance of infectious emboli can be diagnostic when the causative organism is Cundida The white blood cell count is often elevated with an increase in the proportion of immature granulocytes, but leukopenia may occur in association with severe sepsis or because of the patient’s underlying disease. Numerous laboratory techniques have been proposed and used for the diagnosis of catheter-related bloodstream infections.z6 Differences in patient populations and types of catheters, and the lack of consistent definitions and criteria for diagnosis in the various studies, however, have hindered attempts to compare the various The
INFECTIONS
diagnostic methods. In the following paragraphs, we summarize some of the data on the most frequently used techniques. The most common laboratory method for the diagnosis of catheter-related infection is the semiquantitative culture technique, in which a segment (the catheter tip and/or the subcutaneous segment) of the catheter is rolled back and forth on an agar plate four times.3 If 15 or more colony-forming units grow from either segment, the catheter is considered colonized. This technique has a positive predictive value between 10 and 40% and is neither highly sensitive nor highly specific for the prediction of bacteremia, but when used in conjunction with peripheral blood cultures and interpreted in the clinical setting can be helpful.3P23X57 Some investigators have proposed higher cutoff values for the number of colony-forming units that predict bacteremia to increase the specificity of the re~ult,~* whereas others have proposed a lower threshold.5g The clinical impact of the semiquantitative culture on the treatment of the patient was believed to be low in a recent study,6o but this interpretation was not based on comparative data from a randomized trial. other techniques are frequently being proposed and evaluated for better predictive values. Qualitative broth cultures of the catheter tip have a very low positive predictive value and thus have no role in the diagnosis of catheter-related bacteremia.6’ Quantitative cultums of the catheter segment after sonication or vortexing detect organisms present on both the internal and external surfaces of the catheter. Most but not all authors have reported better sensitivity, specificity and predictive values with quantitative than with semiquantitative catheter segment cultures, 57.62B63 and they may be better predictors of catheter-related infection.61.65 Some methods try to avoid removing the catheter for diagnostic purposes because 7590% of intensive care patients with central venous catheters and a new unexplained fever do not have a catheter-related infection and because many catheter-related infections in patients with tunneled catheters can be treated without removal of the catheter. Culture of the skin around the insertion point of the catheter has had good negative predictive value for the diagnosis of catheter-related infection in some studies of shortterm catheters 57.66and had 100% positive predictive value when done in patients with suspected catheter-related infection in patients with nontnnneled catheters.67 Comparison of simultaneous quantitative cultures of blood obtained through a central venous catheter and from a peripheral venipuncture has been used in an attempt to make an in sin4 diagnosis of catheter-related septicemia. The finding of a fivefold increase in the concentration of an organism in catheter blood compared with peripheral blood has correlated well with the presence of catheter-related infection in some studies68-72but not in others?5*73 The results of qualitative blood cultures obtained through the catheter are difficult to interpret because of high rates of false-positive cultures.74.7sTherefore, only peripheral blood cultures need be obtained when suspecting an infected catheter. When the blood cultures grow the same microorganism as the catheter segment culture, the diagnosis of catheter-related bloodstream infection can be safely made, except perhaps for coagulase-negative staphylococci, where molecular typing methods may be necessary to prove the identity of strains isolated from blood and catheter. Catheter hubs are not routinely cultured, thereby missing the source of some infections.57*68~76 I&sates are rarely the source of infection” and, unless there is an apparent outbreak of primaty bloodstream infections, do not need to be routinely c~ltured~~ TREATMENT
signs of infection are present, peripheral blood cultums should be obtained and antibiotics should be statted empirically if the patient is neutropenic or clinically unstable, covIf systemic
CATHETER-RELATED
211
INFECTIONS
ering the most common organisms. If local signs of infection are present in a nontunneled catheter, a gram stain of the exudate may help choose an appropriate antimicrobial agent, and a culture of the exudate should be obtained. The catheter should be removed and cultured, and, if necessary, a new catheter inserted at a different site. When evidence of systemic infection develops without local inflammation at the catheter site in a stable patient, various approaches have been advocated. For short-term use of central catheters, changing the catheter over a guidewire, culturing catheter segments and obtaining peripheral blood cultures is a reasonable approach.r4 A search for other sources of infection should be conducted. If the catheter is found to be significantly colonized, then the catheter that was replaced over a guidewire should be removed and a new one inserted at a different site. Otherwise, the catheter can be left in place. For a patient with a tunneled catheter, one may choose to wait for results of blood cultures if the patient is clinically stable. Tunnel infections usually require removal of the catheter, but exit site infections involving tunneled catheters can often be cured with antibiotics without removing the catheter. For tunneled catheters, infections caused by Candida species, other fungi and certain bacteria (e.g., S. aureus) are more likely to require catheter removal than coagulase-negative staphylococci. Nevertheless, patients with coagulase-negative staphylococcal bacteremia had a significantly higher risk for the recurrence of bacteremia when the catheter remained in place (20%) than patients whose catheters were removed (3%) in one recent studyy7 The decision to remove the catheter must therefore be individualized for each patient. Similarly, the catheter should be removed when there is no clinical improvement after therapy with an appropriate antimicrobial agent for 72 hr, or when the infection of the catheter is associated with septic thrombophlebitis. Duration of antibiotic therapy, in the absence of endocarditis, septic thrombophlebitis or other complicating factors such as prosthetic valves, is commonly l-2 wk. For catheterrelated bacteremia due to S. aureus, there is no consensus on length of therapy,78 but some recent data seem to indicate that a lo- to 15day course may be sufficient in uncomplicated cases.79 For catheter-related candidemia, a 2-wk course with either fluconazole (400 mg/d) or amphotericin B (0.5 0.6 mg. kg-’ *d-l) after the last positive blood culture is sufficient, but removal of the catheter is necessary.80~8’ PREVENTION
A variety of skin antiseptics has been evaluated for their efficacy in decreasing the incidence of catheter colonization. A chlorhexidine gluconate antiseptic solution has been found to be the more effective than alcohol or povidone-iodine for cleansing insertion sites but is not yet available in this country>2-84 Polymyxinneomycin-bacitracin ointment decreases the incidence of catheter colonization by 50% compared with the use of no ointment but predisposes to a fivefold increase in the risk of colonization with Candidu and should not be used on central venous catheters.85,s6 Povidone-iodine ointment was recently shown to provide signifi-
cant protection against catheter-related bloodstream infection when used to dress subclavian dialysis cathetersso The use of transparent dressings instead of gauze dressings has been questioned.*7 A recent meta-analysis concluded that use of transparent dressings on central venous catheters was associated with a significantly elevated relative risk of catheter tip colonization (RR = 1.78, p < 0.001) , with a trend toward an increase in catheter-related bacteremia (RR = 1.63, p = 0.20):’ This may have been due to increased moisture under the dressing favoring bacterial growth. A recent study comparing newer highly permeable polyurethane dressings to commonly used polyurethane or gauze dressings for Swan-Ganz catheters found no increased risk of catheter-related bloodstream infection as compared with gauze but also failed to detect an increased risk with the older style polyurethane dressing as compared with the newer more permeable polyurethane.88 More studies are needed with consistent results before transparent dressings can be routinely recommended for use on short-term central venous catheters. In general, dressing changes every 48-72 h are recommended, but daily inspection and palpation of the exit site are necessary. The entire infusion tubing set should be replaced routinely every 24 h when blood products or lipids are administered. Otherwise, this tubing can be replaced every 72 h.“,W Risk factors discussed earlier should be avoided if possible. Maximal barriers (i.e., sterile long sleeved gowns, large sheet drapes, gloves and masks) should be used to ensure aseptic insertion of central venous catheters.47 Special types of catheters that decrease the rate of catheter-related bacteremia are now available. Short-term catheters with a silver-impregnated cuff are protective with a threefold decrease in colonization of the catheter and a fourfold decrease in catheter-related bactereka.86.90 Antibiotic-coated catheters have shown a similar level of protection in one randomized trial with a, greater than sixfold reduction in the incidence of catheter colonization, but many have expressed concern about using antibiotics commonly used for clinical therapy because of the possible selection of resistant flora.9’ The use of antiseptic-impregnated catheters is an alternative that would bypass this concern, and these have been shown to be effective in reducing the incidence of catheterrelated infection in a randomized tria192and a crossover study93 in intensive care unit patients. A novel approach involving the use of a minocycline-EDTA flush solution for the prevention of catheter infection has recently been described but remains to be evaluated in clinical trials.94 Currently available data do not support the need for scheduled replacement of short-term central venous catheters, either by guidewire exchange or through insertion at a new site.4 Rather, when optimal catheter care is provided, central venous catheters can be kept in place as long as clinically indicated but should be removed as soon as they are no longer necessary for care of the patient. ACKNOWLEDGMENT
Supported in part by National Institutes of Health Training Grant T32AI07046.
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19. Shiro H, Muller E, Gutierrez N, et al. Transposon mutants of Staphylococcus epidemtidis deficient in elaboration of capsular polysaccharide/adhesin and slime are avirulent in a rabbit model of endocarditis. J Infect Dis 1993; 169:1042 20. Takeda S, Pier GB, Kojima Y, et al. Protection against endocarditis due to Staphylococcus epidemzidis by immunization with capsular polysaccharide/adhesin. Circulation 1991;84:2539 21. Clarke DE, Raffin TA. Infectious complications of indwelling longterm central venous catheters. Chest 1990;97:966 22. Ryan JAJ, Abel RM, Abbott WM, et al. Catheter complications in total parenteral nutrition: a prospective study of 200 consecutive patients. N Engl J Med 1974;290:757 23. Snydman DR, Murray SA, Komfeld SJ, Majka JA, Ellis CA. Total parenteral nutrition related infections: prospective epidemiologic study using semiquantitative methods. Am J Med 1982;73:695 24. Barber GR, Brown AE, Kiehn TE, Edwards FF, Armstrong D. Catheter-related Malassezia furfia fungemia in immunocompromised patients. Am J Med 1993;95:365 25. Macias A, Hemandez I, Munoz J, et al. High rate of intravenous fluid contamination in a pediatric unit and procedure for control [abstract 16311. Programs and Abstracts of the 33rd Interscience Conference of Antimicrobial Agents and Chemotherapy. New Orleans, Louisiana, 1993 26. Tully JL, Griedland GH, Baldini LM, Goldmann DA. Complications of intravenous therapy with steel needles and Teflon catheters a comparative study. Am J Med 1981;70:702 27. Tager IB, Ginsberg MB, Ellis SE, et al. An epidemiologic study of the risks associated with peripheral intravenous catheters. Am J Epidemiol 1983; 118:839
28. Maki DG, Ringer M. Evaluation of dressing regimens for prevention of infection with peripheral intravenous catheters gauze, a transparent polyurethane dressing, and an iodophor-transparent dressing. JAMA 1987;258:2396 29. Garland JS, Nelson DB, Cheah T, Hennes HH, Johnson TM..Infectious complications during peripheral intravenous therapy with Teflon catheters: a prospective study. Pediatr Infect Dis J 1987;6:918
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35 Andrivet P, Bacquer A, Vu Ngoc C, et al. Lack of clinical benefit from subcutaneous tunnel insertion of central venous catheters in immunocompromised patients. Clin Znfect Dis 1994; 18:199 36 Clark-Christoff N, Watters VA, Sparks W, et al. Use of triplelumen subclavian catheters for administration of total parenteral nutrition. J Parenteral Enter01 Nutr 1992; 16:403 37. Farkas JC, Liu N, Bleriot JP, et al. Single- versus triple-lumen central catheter-related sepsis: a prospective randomized study in a critically ill population. Am J Med 1992;93:277 38. Maki DG, Stolz S. The epidemiology of central-venous catheterrelated bloodstream infection (BSI) [abstract 5471. Programs and Abstracts of the 34th Interscience Conference of Antimicrobial Agents and Chemotherapy. Orlando, FL, 1994:67 39. Howell PB, Walters PE, Donowitz GR, Farr BM. Risk factors for infection of adult patients with cancer who have tunneled central venous catheters. Cancer 1995;75:1367 40. Danzig L, Short L, Collins K, et al. Bloodstream infections ( BSIs) associated with a needleless intravenous (IV) infusion system used in patients on home infusion therapy [abstract 52001. Programs and Abstracts of the 34th Interscience Conference of Antimicrobial Agents and Chemotherapy. Orlando, Florida, 1994: 195 41. Baxter JK, Babineau TJ, Apovian CM, et al. Perioperative glucose control predicts increased nosocomial infection in diabetics. Crit Care Med 1990; 18:S207
42. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991;325:525 43. Shiro H, Muller E, Takeda S, et al. Potentiation of Staphylococcus epidennidis catheter-related bacteremia by lipid infusions. J Infect Dis 1995; 171:220
44. Kowalewska-Grochowska K, Richards R, Moysa GL, et al. Guidewire catheter change in central venous catheter biotilm formation in a bum population. Chest 1991; 100:1090 45. Badley AD, Steckelberg JM, Wollan PC, Thompson RL. Comparison of the infectious risks of de novo CVP lines and replacement CVP lines [abstract 5481. Programs and Abstracts of the 34th Interscience Conference of Antimicrobial Agents and Chemotherapy. Orlando, FL, 1994:67 46. Rotstein C, Brock L, Roberts RS. The incidence of first Hickman catheter-related infection and predictors of catheter removal in cancer patients. If Control Hosp Epi 1995; 16:451 47. 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; 15:231 48. Williams JF, Seneff MG, Friedman BC, et al. Use of femoral venous catheters in critically ill adults: prospective study. Crit Care Med 1991; 19:550
49. Armstrong CW, Mayhall CG, Miller KB, et al. Prospective study of catheter replacement and other risk factors of infection of hyperalimentation catheters. J Znfect Dis 1986; 154:808 50. Levin A, Mason AJ, Jindal KK, Fong IW, Goldstein MB. Prevention of hemodialysis subclavian vein catheter infections by topical povidone iodine. Kidney Int 1991;40:934 51. Hoffman KK, Weber DJ, Samsa GP, Rutala WA. Transparent polyurethane film as an intravenous catheter dressing: a meta-analysis of the infection risks. JAMA 1992;267:2072 52. Richet H, Hubert B, Nitemberg G, et al. Prospective multicenter study of vascular-catheter-related complications and risk factors for positive patients. J Clin Microbial 1990;28:2520
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INFECTIONS
53. 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 (Suppl 3B):3B-197s 54. Lazarus HM, Creger RJ, Bloom AD, Shenk R. Percutaneous placement of femoral central venous catheter in patients undergoing transplantation of bone marrow. Surg Gynecol Obstet 1990; 170:403 55. Pittet D, Chuard C, Rae AC, et al. Clinical diagnosis of central venous catheter line infections: A difficult job [abstract 4531. In Programs and Abstracts of the 31st Interscience Conference of Antimicrobial Agents and Chemotherapy. Chicago, 1991 56. Pfaller MA. Laboratory diagnosis of catheter-related bacteremia. Infect Dis Clin Pratt 1995;4:206 57. Cercenado E, Ena .I, Rodriguez-Creixems M, Romero I, Bouzza E. A conservative procedures for the diagnosis of catheter-related infections. Arch Intern Med 1990; 150:1417 58. Rello J, Co11P, Prats G. Laboratory diagnosis of catheter-related bacteremia. Stand J Infect Dis 1991;23:583 59. Collignon PJ, Soni N, Pearson IY, et al. Is semiquantitative culture of central vein catheter tips useful in the diagnosis of catheterassociated bacteremia? J Clin Microbial 1986;24:532 60. Widmer AF, Nettleman M, Flint K, Wenzel RP. The clinical impact of culturing central venous catheters. Arch Intern Med 1992; 152:1299 61. Nahass RG, Weinstein MP. Qualitative intravascular catheter tip cultures do not predict catheter-related bacteremia. Diag Microbial Infect Dis 1990; 13:223 62. Raad I, Sabbagh MF, Rand KH, Sheretz RJ. Quantitative tip culture methods and the diagnosis of central venous catheter-related infections. Diagn Microbial Infect Dis 1992; 15: 13 63. Brun-Bruisson C, Abrouk F, Legrand P, et al. Diagnosis of central venous catheter-related sepsis: critical level of quantitative tip cultures. Arch Intern Med 1987; 147873 64. Siegman-Igra Y, Anglim AM, Ada1 KA, Strain BA, Farr BM. Diagnosis of vascular catheter related bloodstream infections (CRBSI) [abstract J53]. Programs and Abstracts of the 34th Interscience Conference of Antimicrobial Agents and Chemotherapy. Orlando, FL, 1994:68 65. Sheretz R, Heard S, Raad I, Gentry L. Culturing catheter tips is an insensitive method for diagnosing triple lumen vascular catheter infection [abstract 8181. Program and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Anaheim, California, 1992 66. Armstrong CW, Mayhall CG, Miller KB, et al. Clinical predictors of infection of central venous catheters used for total parenteral nutrition. Infect Control Hasp Epidemiol 1986; 11~71 67. Raad I, Baba M, Saciolwski M. Diagnosis of catheter related infections (CRI) : the predictive value of surveillance and targeted quantitative skin cultures (QSC). Programs and Abstracts of the 32nd Interscience Conference of Antimicrobial Agents and Chemotherapy. Anaheim, California, 1992 68. Douard MC, Clementi E, Arlet G, et al. Negative catheter-tip culture and diagnosis of catheter-related bacteremia. Nutrition 1994; 10:397 69. Flynn PM, Shenep JL, Barrett FF. Differential quantitation with a commercial blood culture tube for diagnosis of catheter-related infection. J Clin Microbial 1988;26: 1045 70. Flynn PM, Shenep JL, Stokes DC, Barrett FF. In situ management of confirmed central venous catheter-related bacteremia. Pediatr Infect Dis J 1987;6:729 71. Mosca R, Curtas S, Forbes B, Meguid MM. The benefits of isolator cultures in the management of suspected catheter sepsis. Surgery 1987; 102:718 72. Raucher HS, Hyatt AC, Barzilai A, et al. Quantitative blood cultures in the evaluation of septicemia in children with Broviac catheters. J Pediatr 1984; 104:29 73. Paya CV, Guerra L, Marsh HM, et al. Limited usefulness of quantitative culture of blood drawn through the device for diagnosis of intravascular-device-related bacteremia. J Clin Microbial 1989; 27:1431 74. Bates DW, Goldman K, Lee TH. Contaminant blood cultures and resource utilization. JAMA 1991;265:365
213 75. Bryant JK, Stand CL. Reliability of blood cultures collected from intravascular catheter versus venipuncture. Am J Clin Pathol
1987;88:113 76. Jakobsen CJB, Hansen V, Jensen JJ, Grave N. Contamination of subclavian vein catheters: an intmluminal culture method. J Hosp Infect 1989; 13:253 77. Raad 0, Davis S, Khan A, et al. Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bacteremia. Infect Control Hosp Epidemiol 1992; 13:215 78. Jemigan JA, Farr BM. Short-course therapy of catheter-related Staphylococcus aureus bacteremia: a meta-analysis. Ann Intern Med 1993; 119:304 79. Malanoski GJ, Samore MH, Pefanis A, et al. Staphylococcus aureus bacteremia: minimal effective therapy and unusual infectious complications associated with arterial sheath catheters. Arch Intern Med 1995; 155:1161 80. Lecciones JA, Lee JW, Navarro EE, et al. Vascular catheter-associated fungemia in patients with cancer: analysis of 155 episodes. Clin Infect Dis 1992; 14:875 81. Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med 1994; 33 1: 1325 82. Sheehan G, Leicht K, O’Brien M, Taylor G, Rennie R. Chlorhexidine versus povidone-iodine as cutaneous antisepsis for prevention of vascular-catheter infection [abstract 16161. Programs and Abstracts of the 33rd Interscience Conference of Antimicrobial Agents and Chemotherapy. New Orleans, Louisiana, 1993 83. Mimoz 0, Pieroni L, Lawrence C, Edouard A, Samii K. Prospective trial of povidone-iodine (PI) and chlorhexidine (CH) for prevention of catheter-related sepsis (CRS) [abstract 5561. Programs and Abstracts of the 34th Interscience Conference of Antimicrobial Agents and Chemotherapy. Orlando, Florida, 1994 84. Maki DG, Ringer M, Alvarado CJ. Prospective randomized trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991;338:339 85. Maki DG, Band JD. A comparative study of polyantibiotic and iodophor ointments in prevention of vascular catheter-related infection Am J Med 1981;70:739 86. Flowers RH, Schwenzer KJ, Kopel RF, et al. Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheterrelated infection: a randomized, controlled trial. JAMA 1989; 216:878 87. Fitchie C. Central venous catheter-related infection and dressing type. Intensive Crit Care Nurs 1992; 8:199 88. Maki DG, Stolz SM, Wheeler SJ, Mermel LA. A prospective, randomized trial of gauze and two polyurethane dressings for site care of pulmonary artery catheters: implications for catheter management. Crit Care Med 1994;22:1729 89. Sitges-Serra A, Linares J, Perez JL, et al. A randomized trail on the effect of tubing changes on hub contamination and catheter sepsis during parenteral nutrition. J Parenteral Enter01 Nutr 1985;9:322 90. Maki DG, Cobb L, Garman JK, et al. An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multicenter trial. Am J Med 1988; 85:307 91. Kamal GD, Pfaller MA, Rempe LE, Jebson PJR. Reduced intravascular catheter infection by antibiotic bonding. JAMA 1991; 26512364 92. Maki DG, Wheeler SJ, Stolz SM, Mermel LA. Clinical trial of a novel antiseptic central venous catheter [abstract #461]. Programs and Abstracts of the 31st Interscience Conference of Antimicrobial Agents and Chemotherapy. Chicago, Illinois, 1991:176 93. Clemence MA, Anglim AM, Jemigan JA, et al. A study of prevention of catheter related bloodstream infection with an antiseptic impregnated catheter [abstract J199]. Programs and Abstracts of the 34th Interscience Conference of Antimicrobial Agents and Chemotherapy. Orlando, Florida, 1994 94. Raad I, Hachem R, Sherertz R. Minocycline-EDTA (M-EDTA) flush solution for the prevention of vascular catheter infection. Programs and Abstracts of the 34th Interscience Conference of Antimicrobial Agents and Chemotherapy. Orlando, Florida, 1994
Nutrition Vol. 12, No. 3, 1996
Central Venous Catheter-Related A Review KARIM
A. ADAL, MD, MS,* AND BARRY
Infections:
M. FARR, MD, MSc
From the University of Virginia Health Sciences Center, Charlottesville,
Virginia, USA
Date accepted: 27 October 1995 ABSTRACT
Catheter-associated bloodstream infections remain an important cause of nosocomial infection, with an estimated 50,000100,000 cases occurring each year in the United States. Central venous catheters are believed to be responsible for 90% of such infections. The cumulative risk of acquiring a catheter-related bloodstream infection has ranged between 1 and 10% for central venous catheters in general and 6% for total parenteral nutrition catheters. The skin is the most common source of organisms causing catheter-related infections. Recent prospective studies have shown that the incidence density per catheter day does not increase with duration of catheterization and that routine changes, either over a guidewire or by new site puncture, do not appear to lower the risk of infection. Diagnosis of infection can be difficult in intensive care patients but is usually easier in less ill patients with a central venous catheter. Quantitative or semiquantitative laboratory techniques can be used to confirm the diagnosis in the appropriate clinical setting. A variety of preventive measures have been shown to minimize the risk of development of catheter-related bloodstream infection, including use of maximal aseptic technique for insertion, use of special teams for care of the catheter, limiting manipulation of the catheter, use of povidoneiodine ointment and cotton gauze dressings for recently inserted catheters, a silver-impregnated collagen cuff and antisepticimpregnated catheters. Nutrition 1996; 12:208-213 Key words: central venous catheters, complications,
infection, prevention
INTRODUCTION
Intravenous
catheters
are used in more than 50% of hospital-
ized patients in the United States and are increasingly used in the outpatient setting. There is a wide variety of types of central venous catheters. Pulmonary artery catheters are primarily used for hemodynamic monitoring of critically ill patients. Singleor multilumen nontunneled catheters are frequently placed in hospitalized patients for central access. Tunneled catheters and catheters with subcutaneous infusion ports are frequently used for long-term access in patients with cancer or gastrointestinal disease contraindicating enteral feeding.“Peripherally inserted central catheters have primarily been used in patients requiring infusions for an intermediate duration of several weeks to several months but are now being used with increasing frequency in hospitalized patients. Catheter uses include hemodynamic monitoring; the administration of medications, fluids, blood products or total parenteral nutrition and specialized functions such as hemodialysis and plasmapheresis. Serious mechanical and infectious complications can occur as complications, however, and an estimated 50,000- 100,000 catheter-associated
bloodstream infections occur each year in the United States, ’ associated with a mean excess hospital stay of 7 days.* In this review, we summarize current knowledge of infections associated with these catheters, including a discussion of the pathogenesis, risk factors, diagnosis, therapy and methods of prevention. DEFINITIONS
Significant colonization of the catheter is demonstrated by a positive semiquantitative culture ( 15 or more colony-forming units)334 or quantitative culture (greater than lo2 to 10’ colonyforming units)5 of the catheter tip or subcutaneous segment in the absence of local or systemic symptoms and signs of catheter infection. Exit site infection is present either when frank pus is seen at the site where the catheter penetrates the skin or when there is inflammation (erythema, tenderness and induration) within 2 cm of the skin exit site.6 A semiquantitative or quantitative catheter culture would in most instances be positive with exit site infections, but tunneled catheters are not usually removed
*Current affiliation: The Cleveland Clinic Foundation, Cleveland, OH. Correspondence to: Barry M. Farr, MD, MSc, University of Virginia Health Sciences Center, Box 473, Charlottesville, VA 22908, USA.
Nutrition 12:208-213, 1996 OElsevier Science Inc. 1996 Printed in the USA. All rights reserved.
ELSEVIER
0899-9007/96/$15.00 PII: SO899-9007(96)OC!O41-X
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in the presence of an exit site infection. Tunnel infection is present when there are signs of inflammation along the tunnel track of a catheter beyond the first 2 cm from the exit site and laboratory values reveal a positive semiquantitative or quantitative catheter culture.6 Catheter-, catheter hub-, or infusate-related bloodstream infection is present when in the absence of other sources of infection, the same organism is cultured from a percutaneous blood culture and, respectively, a semiquantitative (or quantitative) catheter segment culture, a catheter-hub culture or a culture of the infusate.’ Quantitative blood cultures have also been used to define catheter-related bloodstream infection, with a ratio :, 5 in the concentration of microbes in blood aspirated from a central venous catheter to the concentration in blood from a peripheral vein. PATHOGENESIS
A variety of hypotheses have been proposed to explain the events leading to infection of central catheters.7 Bacterial skin colonization at the catheter-skin interface at the time of insertion or afterward with distal spread of the bacteria along the external catheter surface has been the favored theory for shortterm catheters. Other studies have shown that the introduction of bacteria via the catheter hub due to frequent manipulations is another important means of access to the venous circulation*.’ ; this mode is probably more important for long-dwelling catheters.” Contamination of infusate has been rare in recent years?” Contamination of the antiseptic used to prepare the skin before catheter insertion has occurred, particularly with benzalkonium solutions and other quatemary ammonium compounds.12 Seeding of the catheter at the time of bacteremia from a remote source can cause catheter infection.‘.r3.r4 The mechanism may vary depending on the clinical situation, and more than one mechanism may be responsible in the pathogenesis of some cases of catheter infection. Host factors, catheter composition and an interaction between the microorganisms and the catheter can each play an important role in the pathogenesis of catheter-related bloodstream infections.” The dynamic interaction between microorganisms and the catheter involves a series of related steps, beginning with adherence and followed by colonization and dissemination, Host proteins such as fibronectin coat the catheter rapidly once inserted into the patient, providing a substrate for binding of Staphylococcus aureus but not Staphylococcus epidermidis.L6 Slime-producing S. epidermidis expresses a specific polysaccharide capsular adhesion that mediates attachment to the surface of the catheters ‘7~L8 and to heart valves in a rabbit model.” Mutant strains of S. epidermidis that were deficient in slime and capsular polysaccharide adhesin failed to cause endocarditis in rabbits, I9 and rabbits immunized with the adhesin were protected against endocarditis.20 Slime facilitates bacterial persistence on catheters by helping bacteria evade host defenses and also renders the microbes less susceptible to antibiotics.15 MICROBIOLOGY
The skin is the most common source of organisms causing catheter-related infections.7 Coagulase-negative staphylococci are the bacteria most frequently isolated from catheters, but in most cases this colonization does not progress to bacteremia. On the other hand, the isolation of S. aureus from blood cultures is strongly predictive of a catheter-related bacteremia and is associated with a greater incidence of complications such as endocarditis and osteomyelitis. There is a higher incidence of infection with Corynebacterium and Enterococcus species, gram-negative rods and fungi, in infections of tunneled catheters compared with other cathe-
ters, probably reflecting the decreased immune status of the patients with these types of catheters and perhaps the high frequency of antimicrobial exposure which selects for antibiotic-resistant organisms. 21 Candida species and staphylococci are frequent etiologic agents in patients receiving total parenteral nutrition.22.23Malassezia ji&r is mostly seen in neonates receiving intravenous lipid emulsion but can also occur in adults.24 Hematogenous dissemination from another site of infection accounts for greater than 50% of yeast infections, as well as most infections due to enterococcal and gram-negative organisms (e.g., E. coli and Klebsiella species) .5 In the rare infusaterelated infection or infection due to contaminated disinfectant, the organisms are usually gram-negative bacteria that can grow well in such solutions (e.g., Enterobacter, Klebsiella and Pseudomonas species) .25 EPIDEMIOLOGY
AND RISK FACTORS
important risk factor for the development of a catheterrelated infection may be the type of catheter used. The risk of bloodstream infection from a peripheral intravenous catheter is extremely low, less than one bacteremia per 1000 catheters.26-29 By contrast, the risk of acquiring a catheter-related bloodstream infection from nontunneled central venous catheters ranges between 1 and 10% of such catheter insertions, ’and central catheters are believed to account for 90% of catheter-related bloodstream infections.3o Peripherally inserted central catheters have had a low incidence of bacteremia in outpatients3’.32and are much easier to remove than tunneled catheters that require a surgical procedure. Their use in inpatients has not been investigated in randomized trials but may have a low rate of infections as we11?3,” Tunneled catheters and catheters with subcutaneous infusion ports have been associated with an acceptably low incidence of catheter-related bacteremias, but insertion costs are high.3’ Two recent studies have raised questions as to whether tunneling catheters result in lower rates of infection for long-term access. A randomized multicenter trial in France did not find a lower rate for tunneled catheters,35 and a large cohort study of cancer patients at the M.D. Anderson Cancer Center found lower rates with nontunneled subclavian catheters as compared with rates reported for tunneled catheters in cancer patients.31 Several observational studies have reported higher rates of infection with multilumen catheters, and one randomized trial of catheters used for total parenteral nutrition also found a higher rate of infection with multilumen catheters.36 Because study methods stated that two of the lumens of the triple lumen catheters could be used for other infusions and for blood drawing, however, there appeared to be greater chance for manipulation and contamination of the triple lumen catheter than of the single lumen catheter in this trial, and adherence to a protocol for aseptic catheter access was described as “voluntary.” A second randomized trial found no association with multilumen catheters,37 leaving uncertainty as to the importance of multiple lumens. One recent study involving multilumen catheters in intensive care patients reported that only 2% of catheterizations resulted in bloodstream infection, and that there was no association between total parenteral nutrition and infection.4 Catheters used for total parenteral nutrition have been considered to be at higher risk for catheter-related bloodstream infection. Use of a total parenteral nutrition catheter for infusion of other products has been associated with an increased risk of infection?3 However, a decrease in the occurrence of infection from approximately 2530% to 3-5% has been shown to occur with the institution of a dedicated team for the insertion and maintenance care of the alimentation line.’ Three recent studies of the epidemiology of central venous catheter-related bloodstream infection among intensive care patients and cancer patients found no associOne
210
CATHETER-RELATED
ation with parenteral nutrition,4~38~3g suggesting that the team approach to maintenance cam could possibly be valuable for central venous catheters used for other purposes as well. The need to use sterile techniques in handling hyperalimentation fluids and lines is paramount. A needleless intravenous infusion system used for total parenteral nutrition was associated with an increased risk of bloodstream infection in a recent study.4o It is interesting to note that poor glucose control in diabetics has been correlated with a higher incidence of postoperative infections, including bacteremias.4’ This may explain in part the different rates of postoperative infectious complications in a study of surgical patients receiving total parenteral nutrition in which hyperglycemia occurred significantly more in patients randomized to total parenteral nutrition.” Limiting lipid infusions may also decrease the incidence of catheter-related infections?3 More research is needed regarding the effect of metabolic variables on the incidence of catheter infections. Duration of catheterization is an important risk factor for catheter-related bacteremia.g For this mason, several authorities have recommended changing the catheter routinely every few days. Recent prospective studies, however, have shown that the incidence density per catheter day does not increase with increasing duration of catheterization and that routine changes, either over a guidew~e4,3*.44.45 or by new site pun~ture,~~~~do not appear to lower the risk of infection. Regular guidewire exchanges may actually increase the risk of infection.4~38”5 Neutropenia is a significant risk for infections in general, and in one recent study of cancer patients with tunneled central catheters, it was the only independent risk factor for catheter infection.3g Another study found that hematologic neoplasms were significant risk factors for catheter infection,46 but neutropenia was not assessed as an independent variable and is known to occur more frequently with hematologic neoplasms. Male sex was also suggested to be a risk factor in the latter study, but this has not been demonstrated in previous studies and would require confirmation. The use of strict aseptic procedures for the insertion of the catheter has resulted in a lower risk of subsequent catheter infection.47 In two studies, the risk of infection was inversely proportional to the number of previous catheters inserted by the physician.48V4g Subsequent catheter care such as the use of povidoneiodine ointment5’ and gauze dressings” has been associated with a decrease in the risk of catheter-related infection in some studies. Observational studies have generally shown lower rates with subclavian placement than with placement in the internal jugular or femoral vein,‘253 but not all studies have shown high rates with the latter two approaches.48*” Intensive care is associated with an increased number of catheter manipulations for hemodynamic monitoring that in turn is associated with an increased risk of catheter-related bloodstream infections.23 CLINICAL FEATURES AND DIAGNOSIS
diagnosis of catheter-related bloodstream infection can be difficult. Local clinical signs such as tenderness, erythema or pumlence are present in only about 30% of cases involving central catheters.s5 The most common manifestation is fever alone, but hypothermia, rigors, tachypnea, hypotension and/or confusion may also be present. A careful ophthahnoscopic examination must be performed because the appearance of infectious emboli can be diagnostic when the causative organism is Cundida The white blood cell count is often elevated with an increase in the proportion of immature granulocytes, but leukopenia may occur in association with severe sepsis or because of the patient’s underlying disease. Numerous laboratory techniques have been proposed and used for the diagnosis of catheter-related bloodstream infections.z6 Differences in patient populations and types of catheters, and the lack of consistent definitions and criteria for diagnosis in the various studies, however, have hindered attempts to compare the various The
INFECTIONS
diagnostic methods. In the following paragraphs, we summarize some of the data on the most frequently used techniques. The most common laboratory method for the diagnosis of catheter-related infection is the semiquantitative culture technique, in which a segment (the catheter tip and/or the subcutaneous segment) of the catheter is rolled back and forth on an agar plate four times.3 If 15 or more colony-forming units grow from either segment, the catheter is considered colonized. This technique has a positive predictive value between 10 and 40% and is neither highly sensitive nor highly specific for the prediction of bacteremia, but when used in conjunction with peripheral blood cultures and interpreted in the clinical setting can be helpful.3P23X57 Some investigators have proposed higher cutoff values for the number of colony-forming units that predict bacteremia to increase the specificity of the re~ult,~* whereas others have proposed a lower threshold.5g The clinical impact of the semiquantitative culture on the treatment of the patient was believed to be low in a recent study,6o but this interpretation was not based on comparative data from a randomized trial. other techniques are frequently being proposed and evaluated for better predictive values. Qualitative broth cultures of the catheter tip have a very low positive predictive value and thus have no role in the diagnosis of catheter-related bacteremia.6’ Quantitative cultums of the catheter segment after sonication or vortexing detect organisms present on both the internal and external surfaces of the catheter. Most but not all authors have reported better sensitivity, specificity and predictive values with quantitative than with semiquantitative catheter segment cultures, 57.62B63 and they may be better predictors of catheter-related infection.61.65 Some methods try to avoid removing the catheter for diagnostic purposes because 7590% of intensive care patients with central venous catheters and a new unexplained fever do not have a catheter-related infection and because many catheter-related infections in patients with tunneled catheters can be treated without removal of the catheter. Culture of the skin around the insertion point of the catheter has had good negative predictive value for the diagnosis of catheter-related infection in some studies of shortterm catheters 57.66and had 100% positive predictive value when done in patients with suspected catheter-related infection in patients with nontnnneled catheters.67 Comparison of simultaneous quantitative cultures of blood obtained through a central venous catheter and from a peripheral venipuncture has been used in an attempt to make an in sin4 diagnosis of catheter-related septicemia. The finding of a fivefold increase in the concentration of an organism in catheter blood compared with peripheral blood has correlated well with the presence of catheter-related infection in some studies68-72but not in others?5*73 The results of qualitative blood cultures obtained through the catheter are difficult to interpret because of high rates of false-positive cultures.74.7sTherefore, only peripheral blood cultures need be obtained when suspecting an infected catheter. When the blood cultures grow the same microorganism as the catheter segment culture, the diagnosis of catheter-related bloodstream infection can be safely made, except perhaps for coagulase-negative staphylococci, where molecular typing methods may be necessary to prove the identity of strains isolated from blood and catheter. Catheter hubs are not routinely cultured, thereby missing the source of some infections.57*68~76 I&sates are rarely the source of infection” and, unless there is an apparent outbreak of primaty bloodstream infections, do not need to be routinely c~ltured~~ TREATMENT
signs of infection are present, peripheral blood cultums should be obtained and antibiotics should be statted empirically if the patient is neutropenic or clinically unstable, covIf systemic
CATHETER-RELATED
211
INFECTIONS
ering the most common organisms. If local signs of infection are present in a nontunneled catheter, a gram stain of the exudate may help choose an appropriate antimicrobial agent, and a culture of the exudate should be obtained. The catheter should be removed and cultured, and, if necessary, a new catheter inserted at a different site. When evidence of systemic infection develops without local inflammation at the catheter site in a stable patient, various approaches have been advocated. For short-term use of central catheters, changing the catheter over a guidewire, culturing catheter segments and obtaining peripheral blood cultures is a reasonable approach.r4 A search for other sources of infection should be conducted. If the catheter is found to be significantly colonized, then the catheter that was replaced over a guidewire should be removed and a new one inserted at a different site. Otherwise, the catheter can be left in place. For a patient with a tunneled catheter, one may choose to wait for results of blood cultures if the patient is clinically stable. Tunnel infections usually require removal of the catheter, but exit site infections involving tunneled catheters can often be cured with antibiotics without removing the catheter. For tunneled catheters, infections caused by Candida species, other fungi and certain bacteria (e.g., S. aureus) are more likely to require catheter removal than coagulase-negative staphylococci. Nevertheless, patients with coagulase-negative staphylococcal bacteremia had a significantly higher risk for the recurrence of bacteremia when the catheter remained in place (20%) than patients whose catheters were removed (3%) in one recent studyy7 The decision to remove the catheter must therefore be individualized for each patient. Similarly, the catheter should be removed when there is no clinical improvement after therapy with an appropriate antimicrobial agent for 72 hr, or when the infection of the catheter is associated with septic thrombophlebitis. Duration of antibiotic therapy, in the absence of endocarditis, septic thrombophlebitis or other complicating factors such as prosthetic valves, is commonly l-2 wk. For catheterrelated bacteremia due to S. aureus, there is no consensus on length of therapy,78 but some recent data seem to indicate that a lo- to 15day course may be sufficient in uncomplicated cases.79 For catheter-related candidemia, a 2-wk course with either fluconazole (400 mg/d) or amphotericin B (0.5 0.6 mg. kg-’ *d-l) after the last positive blood culture is sufficient, but removal of the catheter is necessary.80~8’ PREVENTION
A variety of skin antiseptics has been evaluated for their efficacy in decreasing the incidence of catheter colonization. A chlorhexidine gluconate antiseptic solution has been found to be the more effective than alcohol or povidone-iodine for cleansing insertion sites but is not yet available in this country>2-84 Polymyxinneomycin-bacitracin ointment decreases the incidence of catheter colonization by 50% compared with the use of no ointment but predisposes to a fivefold increase in the risk of colonization with Candidu and should not be used on central venous catheters.85,s6 Povidone-iodine ointment was recently shown to provide signifi-
cant protection against catheter-related bloodstream infection when used to dress subclavian dialysis cathetersso The use of transparent dressings instead of gauze dressings has been questioned.*7 A recent meta-analysis concluded that use of transparent dressings on central venous catheters was associated with a significantly elevated relative risk of catheter tip colonization (RR = 1.78, p < 0.001) , with a trend toward an increase in catheter-related bacteremia (RR = 1.63, p = 0.20):’ This may have been due to increased moisture under the dressing favoring bacterial growth. A recent study comparing newer highly permeable polyurethane dressings to commonly used polyurethane or gauze dressings for Swan-Ganz catheters found no increased risk of catheter-related bloodstream infection as compared with gauze but also failed to detect an increased risk with the older style polyurethane dressing as compared with the newer more permeable polyurethane.88 More studies are needed with consistent results before transparent dressings can be routinely recommended for use on short-term central venous catheters. In general, dressing changes every 48-72 h are recommended, but daily inspection and palpation of the exit site are necessary. The entire infusion tubing set should be replaced routinely every 24 h when blood products or lipids are administered. Otherwise, this tubing can be replaced every 72 h.“,W Risk factors discussed earlier should be avoided if possible. Maximal barriers (i.e., sterile long sleeved gowns, large sheet drapes, gloves and masks) should be used to ensure aseptic insertion of central venous catheters.47 Special types of catheters that decrease the rate of catheter-related bacteremia are now available. Short-term catheters with a silver-impregnated cuff are protective with a threefold decrease in colonization of the catheter and a fourfold decrease in catheter-related bactereka.86.90 Antibiotic-coated catheters have shown a similar level of protection in one randomized trial with a, greater than sixfold reduction in the incidence of catheter colonization, but many have expressed concern about using antibiotics commonly used for clinical therapy because of the possible selection of resistant flora.9’ The use of antiseptic-impregnated catheters is an alternative that would bypass this concern, and these have been shown to be effective in reducing the incidence of catheterrelated infection in a randomized tria192and a crossover study93 in intensive care unit patients. A novel approach involving the use of a minocycline-EDTA flush solution for the prevention of catheter infection has recently been described but remains to be evaluated in clinical trials.94 Currently available data do not support the need for scheduled replacement of short-term central venous catheters, either by guidewire exchange or through insertion at a new site.4 Rather, when optimal catheter care is provided, central venous catheters can be kept in place as long as clinically indicated but should be removed as soon as they are no longer necessary for care of the patient. ACKNOWLEDGMENT
Supported in part by National Institutes of Health Training Grant T32AI07046.
REFERENCES Maki DC. Infections due to infusion therapy. In: Bennet JV, Brachman PS, eds. Hospital infections, 2nd ed. Boston, MA: Little, Brown, 1992:849 Haley RW, Schaberg DR, Crossley KB, Von Allmen SD, McGowan JE. Extra charges and prolongation of stay attributable to nosocomial infections: a prospective interhospital comparison. Am J Med 1981;70:51 Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method for identifying intravenous-catheter-related infection. N Engl J Med 1977;296:1305 Cobb DK, High KP, Sawyer RG, et al. A controlled trial of sched-
uled replacement of central venous and pulmonary-artery catheters. PI Engl J Med 1992:327:1062 5. Hampton AA, Sheretz RJ. Vascular-access infections in hospitalized patients. Surg Clin North Am 1988;68:57 6. Press OW, Ramsey PG, Larson EB, Fefer A, Hickman RO. Hickm$an catheter infections in patients with malignancies. Medicine 1984;63:189
7. Widmer A. IV-related infections. In: Wenzel RP, ed. Prevention and control of nosocomia,l infections. Baltimore, MD: Williams & Wilkins, 1993556 8. Linares .I, Sitges-Serra A, Garau J, Perez JL, Martin R. Pathogenesis
212
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