Infectious complications of indwelling vascular catheters.

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STATE-OF-THE-ART CLINICAL ARTICLE

Infectious Complications of Indwelling Vascular Catheters Issam I. Raad and GeraldP. Bodey

Epidemiology Compared with small peripheral venous or arterial catheters, short-term noncuffed central venous catheters (CYCs) are associated with the highest rate of septicemia, which ranges from 4% to 14% [5-8]. On the basis of recent data, it has been estimated that 3 million CYCs are inserted annually in the United States, and assuming only a 4% rate of septicemia, one would expect at least 120,000 cases ofCYCrelated septicemia each year [8]. This figure does not include sepsis related to peripheral vascular or pulmonary artery catheters. It is, therefore, not surprising that vascular catheters are a major source of nosocomial sepsis and contribute to the majority of nosocomial cases of septicemia due to Staphylococcus epidermidis, Staphylococcus aureus, and Candida species [9, 10]. Given the magnitude and seriousness of the problem, a clear understanding of the diagnosis, pathogenesis, prevention, and treatment of catheter-related infections is essential for health professionals involved in the care of hospitalized patients. The majority of these infections are reversible if one knows how to appropriately diagnose, treat, and resolve these infectious complications.

Diagnosis The terms catheter-related infections and catheter-associated infections have been used by different investigators to

mean different things, which has led to confusion and difficulty in comparing the results of clinical studies. Although standard, well-accepted definitions of these terms do not exist, a clear understanding of the most commonly used ones is important for a reasonable interpretation of the literature. Catheter-related infections can be divided into two main entities: local catheter infections and systemic catheter-related septicemias. Local Catheter Infection

Any of the following conditions can be considered a local catheter infection. An exit- or insertion-site infection. Purulence around the catheter insertion site in the absence of a bloodstream infection represents a local exit- or insertion-site infection. Inflammation around the exit or insertion site that consists of erythema, warmth, tenderness, and swelling is suggestive of, but not specific for, an infection. Inflammation can represent a sterile mechanical condition, particularly when associated with peripherally inserted central catheters. A quantitative culture of the skin or subcutaneous catheter segment may help in distinguishing a sterile inflammation from an exit tunnel infection. Tunnel infection. This condition is characterized by a spreading cellulitis around the subcutaneous tunnel tract of tunneled long-term catheters, such as Hickman-Broviac catheters [11]. Significant catheter colonization. Maki et al. [12] have demonstrated a strong correlation between the isolation of ~ 15 cfu of an organism from a catheter segment and inflammation of skin around a catheter insertion site. Because of this relationship, the term local infection has often been used when ~ 15 cfu are isolated from a catheter segment with use of the roll-plate culture technique [13, 14]. Other investigators have used the term colonization to describe this entity in contradistinction to contamination when < 15 cfu are isolated. Systemic Catheter-Related Septicemia

Received 14 February 1992; revised 28 April 1992. Reprints or correspondence: Dr. Issam Raad, Infectious Diseases (Box 47), The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.

Clinical Infectious Diseases 1992;15:197-210 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1502-0001$02.00

Systemic catheter-related septicemia has often been used as a diagnosis of exclusion to describe a bloodstream infection caused by an organism from the skin of a patient with a vascular catheter who has clinical manifestations of sepsis and no apparent source for the septicemia (such as pneumonia, a wound, or a urinary tract infection) except the catheter

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Yascular catheters are the most frequently used indwelling medical devices and have become necessary tools for the successful treatment of patients with chronic or critical illness. It is estimated that vascular catheters are inserted in more than 20 million patients who are admitted to hospitals in the United States each year [1]. Several complications, however, prevent the prolonged maintenance of vascular catheters. Infection is one of the leading complications, and catheter-related septicemia represents the most frequent lifethreatening complication of vascular catheters [2-4].

From the Section of Infectious Diseases, Department of Medical Specialties, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

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Table 1. Proposed diagnostic definitions of catheter-related septicemia. Probable catheter-related sepsis or (primary) septicemia A common skin organism,* S. aureus, or Candida isolated from one or more blood cultures from a patient with clinical manifestations of sepsis (fever, chills, or hypotension) and no apparent source for the sepsis except the catheter Definite catheter-related sepsis First-degree septicemia (caused by any organism) for which there is clinical or quantitative microbiological evidence implicating the catheter as the source of the sepsis; this evidence consists of anyone of the following four criteria: Pus at the insertion site; isolation of the same organism from the pus and the bloodstream Clinical sepsis that is refactory to antibiotics but that resolves after catheter removal Positive quantitative catheter culture with isolation of the same organism from the catheter and bloodstream Differential quantitative blood cultures with ~ IO-fold colony count of organisms isolated from blood drawn through a central catheter and simultaneously from peripheral venous blood cultures

[15, 16]. This diagnosis ofexclusion is better termed primary nosocomial bloodstream infection (as defined by the Centers for Disease Control [Atlanta]) or probable catheter-related septicemia [17]. Definite catheter-related septicemia is a primary bloodstream infection in which clinical or quantitative microbiological evidence implicates the catheter as a definite source of the infection (table I). The clinical evidence implicating the catheter as a source of infection could be either of the following: (I) an exit-site or tunnel infection due to the same organism (same species and antibiogram) as that isolated from the insertion-site discharge and the bloodstream or (2) resolution of the clinical sepsis (fever and chills) within 48 hours of catheter removal while the patient is receiving no active antibiotics or after an unsuccessful trial of active antibiotics for at least 72 hours. The quantitative microbiological evidence that is necessary to implicate the catheter as the source of primary nosocomial bacteremia includes the results of either quantitative catheter cultures or quantitative blood cultures. Quantitative Catheter Cultures With use ofquantitative catheter cultures, the same organism is isolated from the catheter and the bloodstream. The level of positivity depends on the quantitative culture technique used [18]. The roll-plate semiquantitative culture technique is the simplest and most commonly used method. Several studies have demonstrated the usefulness of the roll-plate technique in diagnosing CVC-related septicemia [18-20]. The limitation of this technique is that only the external surface of the catheter is cultured [21]. After prolonged placement and excessive use of the catheter hub, intraluminal colonization of the CVC becomes equal to or greater than that of the external surface, which is why other quantitative catheter culture techniques might be useful [21]. The flush technique first described by Cieri et al. [22]

quantitates the number of colonies that could be flushed from the internal surface of a catheter. Organisms can be isolated from the internal and external surfaces of catheters with use of the sonication, vortex, and centrifugation techniques; these techniques yield a large number of colonies and are highly sensitive in diagnosing catheter-related septicemia [23-25]. In three clinical studies [25-27], we tested the sonication technique alone and in comparison with the roll-plate technique and found it to be highly diagnostic. However, the limitation of all quantitative catheter culture techniques is that the diagnosis is always retrospective; the clinician has to remove or exchange the catheter to culture the colonies. A recent study of 359 CVCs removed at M. D. Anderson Cancer Center demonstrated that of the 91 CVCs removed because of suspected catheter-related sepsis, only eight (8.8%) were associated with such a diagnosis, and only 17 ( 18.7%) were colonized [28]. All catheters were cultured with use of the roll-plate and sonication techniques. Because of the high rate of unnecessary and wasteful removal ofcatheters, interest has developed in in situ cultures such as the quantitative-brush catheter culture and quantitative blood cultures [29]. Quantitative Blood Cultures For quantitative blood cultures, simultaneous blood samples are drawn through the catheter and a peripheral vein without removal or exchange of the catheter [30]. When the number of organisms obtained through the CVC is severalfold greater than that quantitated from a peripheral blood culture, catheter-related sepsis is diagnosed. Several investigators have performed simultaneous quantitative blood cultures and found that a differential colony count of 10:I (eVC specimen vs. that from the peripheral vein) is indicative of catheter-related septicemia [31-35]. Few other stud-


* Common skin organisms include coagulase-negative staphylococci, micrococci, and Bacillus, Corynebacterium, and Propionibacterium species.

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Pathogenesis There are four potential sources for catheter colonization and cathete r-related sepsis: the skin insertion site, the catheter hub , hematogenous seeding ofthe catheter, and infusate cont amination. T he skin insertion site an d the cathe ter hub are by far the two most important sources. For short-term catheters (including short-term CVC and arterial cath eters), there is a strong correlation among a high level of colonization at the skin insertion site, external catheter colonization , and catheter-related sepsis [23]. It has been suggested that bacteria (coagulase-negative staphylococci and S. aureusy migrate from the exit site along the intercut aneous tract and the external surface of the catheter, thereby causing a high level of colon ization of the distal vascular segment (tip) and ultimately resultin g in catheter-related bacteremia [9]. Maki [43] has shown that the skin is the most common source for short-term catheter colonization and infection . Thi s is why factors that decrease the coloni zation of the insert ion site (such as topical antibiotics and disinfectants [44-46]) and those that interrupt the intercutaneous migration of organisms (such as the silver cuff or dacron sheath cuff [13]) decrease the risk of acquiring catheter-related infections. On the other hand , factors that tend to increase the multipl ication of organisms at the insertion site (such as a transparent plastic dressing [47]) and that lead to its conta mination (for example , heavily contaminated disinfectants [48, 49]) increase the risk of developing catheter-related infections. The catheter hub is another source of colonization of the

Figure 1. Scanning electron microscopic image of the internal surface of a central venous silicone catheter segment from a patient with catheter-related Staphylococcus aureus bacteremia. The white arrow points to the biofilm , and the blackarrow points to the coccal forms representing adherent staphylococcal organisms (bar. 5 /Lm ; X 5.000).

catheter lumen . Organisms can be introdu ced into the hub from the hands of medical personn el. From this contaminat ed hub the organisms migrate along the internal surface of the catheter. where they create a bloodstream infection. Sitges-Serra and co-workers highlighted the hub as the most comm on source of catheter-related septicemia [50-52], while Maki found the hub to be the second most commo n source of catheter-related infection s [43]. This discrepancy could be related to the fact that Maki studied short-t erm catheters that were in place for a mean dur ation of 7.2-9.1 days. whereas the Sitges-Serra group studied longer term CVCs that were in place for a mean durati on of 23.4-26.5 days. At the Uni versity of Tex as M. D. Anderson Ca ncer Center. we used quantitative scanning and tran smission electron microscopy to study the degree ofbiofilm formation and ultra structural colonization on the intern al and extern al surfaces of the CVC (figure 1). For C v'Cs that were relatively short term (mean dur ation . 15 days), both surfaces were colo-


ies have reported a discrepancy between positive semiquantitative catheter cultures and differential quantitative blood cultures [20, 36]. The discrepancy could be partl y explained by the fact that when samples for quantitative blood cultures are drawn through the CVe, organisms are retrieved from the internal surface of the catheter, although when the semiquantitative roll-plate technique is used, only the external surface is cultured. Stain ing of catheters with a gram stain or acridine orange stain has been proposed as a rapid method for the diagnosis of cath eter-related infection s. Cooper and Hopkin s [37] found the gram-stain method to be highly diagno stic but reported the need for at least 15 minutes of microscopi c scanning of the catheter surface. Zuffery et al. [38] used direct acridine staining and reported high sensitivity, specificity, and predictive values (all ;;>84%). Other studies have reported a low-positive predictive value (44%- 48%) for the two staining methods [39, 40]. These staining meth ods are considered experimental at this point because they are labor inten sive and of possible low-positive predictive value. Other quantitat ive techniques. such as the quantitative insertionsite culture, have been proposed [41. 42]. These cultures are of high-negative predic tive value if catheter exit-site inflammation is absent.

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Several prospective studies in which quantitative catheter cultures were used have shown that the three most common types of organisms causing catheter-related infections are coagulase-negative staphylococci, S. aureus, and Candida species [18-28]. C. albicans, followed by C. parapsilosis, accounts for most of the Candida species causing catheter-related infections. Coagulase-negative staphylococci and S. aureus are introduced from the skin insertion site and the hands of medical personnel who contaminate the hub, while one-halfofthe Candida species are thought to seed hematogenously from the gastrointestinal tract and adhere to the fibrin and fibronectin on the surface ofthe catheter [9, 21]. Corynebacterium, especially JK strains, and Bacillus species can cause catheter-related infections, and they are usually introduced from the skin or catheter hub. Gram-negative bacilli acquired from the hospital environment, such as Acinetobacter species, Pseudomonas species, and Xanthomonas maltophilia, have also been reported to cause catheter-related sepsis [76, 77]. Enteric organisms such as Escherichia coli, Klebsiella pneumoniae, and enterococci rarely cause catheterrelated infections.

Prevention The prevention of any nosocomial infection involves a cost-effective, concentrated effort by health care workers to minimize the risk factors and maximize the protective factors. Several factors have been associated with an increased risk of catheter-related infections (table 2). Prolonged catheterization is one of the major risk factors for infection associated with venous and arterial catheters. Figure 2 demonstrates the increased risk of infection (local or disseminated) as it is related to the duration ofcatheterization with indwelling peripheral arterial and Swan-Ganz catheters at M. D. Anderson Cancer Center. Several other studies have shown a strong relationship between prolonged catheterization and arterial catheter-related or CVC-related infections [78-83]. Catheter material may be an important factor in promoting thrombogenesis and adherence of organisms. Linder and colleagues [84] have demonstrated that flexible silicone and polyurethane catheters are less thrombogenic than polyvinylchloride catheters. Other investigators have shown that staphylococci and fungi are more prone to adhere to polyvinylchloride surfaces than to Teflon [74, 75]. Several investigators have suggested that triple-lumen CVCs are associated with a higher risk of infection than are single-lumen CVCs [85-90]. However, other trials have failed to demonstrate any significant difference in infection rates [8, 91, 92]. The location of the catheter could also affect susceptibility; for example, a higher infection rate has been reported for CVCs than for arterial or short peripheral catheters. Hampton and Sherertz [21] reviewed 30 prospective clinical studies involving pulmonary artery, peripheral arterial, short peripheral venous, and central venous cath-


nized to an equal extent [53]. For long-term CVCs (mean duration, 109 days), the degree of colonization and biofilm formation on the internal surface were at least twice those on the external surface [27]. It is, therefore, possible that prolonged use of the CVC hub would result in a high degree of internal surface colonization that would exceed the external surface colonization originating from the insertion skin site. Hematogenous seeding of the CVC from a distant focus (such as the lung or gastrointestinal and urinary tracts) has been suggested [54, 55]. The contribution ofseeding to catheter colonization and sepsis is minimal and has rarely been demonstrated. Electron microscopic studies of CVCs removed from patients with non-CVC-related bacteremia failed to reveal any seeding of the CVC with organisms compatible with those that caused the preceding bacteremia [53]. Several epidemics of infusion-related bacteremia have been related to contaminated infusate [56-58]. Unlike other cases of catheter-related septicemia in which staphylococci and Candida species are the most common etiologic organisms, infusion-related sepsis due to contaminated infusate is often caused by gram-negative bacilli, such as Enterobacter, Pseudomonas, Citrobacter, and Serratia species. Parenteral nutrition solutions and lipid emulsion can promote the growth of many bacteria and fungi [59-61 ], such as Candida parapsilosis and Malassezia furfur. Although many epidemics of nosocomial bacteremia have been caused by contaminated infusate, the contribution of such a source to endemic nosocomial primary bacteremia is very low [43]. Adherence of the bacteria to the catheter surface depends on the interaction of three factors: the host, the microbial factors, and the catheter material. First, the host reacts to the catheter as a foreign body by forming a thrombin sleeve around it [62, 63]. This layer of the host biofilm is rich in fibrin and fibronectin, two substances that are tightly adhered to by S. aureus and Candida species [64, 65]. Both S. aureus and Candida albicans are coagulase-producing organisms that benefit from the process of thrombogenesis in adhering tightly to the fibrin-rich layer of the biofilm. Coagulase-negative staphylococci adhere to fibronectin but not to fibrin [65]. Second, the microbial factors consist of the production of fibrous glycocalyx. Microbial organisms, particularly slime-producing coagulase-negative staphylococci, enhance their adherence by producing a fibrous glycocalyx, also known as extracellular slime, that constitutes the microbial substance of the biofilm [66-69]. The biofilm layer made of microbial and host substances is conducive not only to the adherence of the organisms, but also to their maintenance because it acts as a barrier that protects embedded organisms from antibiotics, phagocytic neutrophils, macrophages, and antibodies [70-73] (figure I). The third factor that plays a role in the adherence process is the catheter material. Several investigators have shown, for example, that S. aureus and Candida species adhere better to polyvinylchloride catheters than to Teflon catheters [74, 75].



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Table 2. Risk and protective factors associated with catheter-related infection. Risk factors

Protective factors

Prolonged catheterization Frequent manipulations Transparent plastic dressings Contaminated skin solutions Improper aseptic techniques* Catheter material Number of catheter lumens Location of catheter

Insertion/maintenance of catheter by infusion therapy team Use of topical disinfectants and antibiotics Use of silver-impregnated cuff Coating catheters with antimicrobial agents

* During

insertion or maintenance.

100 Q

w ~

U

W

II.

~

...

SWAN-GANZ

•

PERIPHERAL ARTERIAL

80

80

~

Z

W

U

a:

40

w a20

o

3

8

9

12

15

18

21

DAYS Figure 2. Life-table analysis of the cumulative risk of developing a catheter-related infection based on the duration ofcatheterization with 71 peripheral arterial catheters and 71 Swan-Ganz catheters inserted at M. D. Anderson Cancer Center.

enced staff, and use of cutdowns for the insertion of catheters [98]. Several protective and preventive methods have been suggested to guard against infection. To avoid improper insertion and maintenance by inexperienced health care workers, several centers have established an expert infusion-therapy team for the insertion and maintenance of catheters. Several studies have shown that such a team can decrease the infection rate fivefold to eightfold [99, 100]. In addition, the team can be cost-effective in centers with high rates of catheter-related infections or with a large volume ofimmunosuppressed patients. At M. D. Anderson Cancer Center, for example, the infection rate for and the durability ofnon tunneled, noncuffed, Silastic CVCs (infection rate, 0.13/ I00 catheter days; mean in-place duration, 109 days) were comparable with those of the tunneled Hickman CVC [28]. We attribute this low rate partly to the availability of an expert infusion-therapy team. Another preventive method consists of lowering the microbial burden at the skin insertion site. Povidone-iodine ointment applied to the insertion site has not been shown to significantly decrease the rate of catheter-related infections [45]. However, topical antibiotics (such as polymyxin in combination with neomycin and bacitracin) have significantly decreased the total risk of acquiring catheter-related infections, although at the expense of the higher risk of acquiring fungal (candidal) colonization and infection [44, 45]. In a three-arm trial, Maki and co-workers [46] compared the effectiveness of 70%alcohol, 10% povidone-iodine, and 2%chlorhexidine gluconate. The rate of catheter-related bacteremia was almost fourfold lower in the chlorhexidine gluconate arm than in the other two arms. Several studies have shown that the attachable silver-impregnated cuff can reduce the incidence of catheter-related infections among critically ill patients with short-term CVCs (mean in-place duration, 5.6-9.1 days) [13. 14]. The silver cuff failed to protect against infections in patients who had the longer-term CVCs in place (mean duration, 20 days) [ 10I] or in patients who had the long-term tunneled Hickman catheters in place [l02].


eters. They evaluated the risk ofinfection per day ofcatheterization. This risk was 1.3% per day for peripheral plastic venous catheters, 1.9% for peripheral arterial catheters, and 3.3%for CVCs. Some investigators have suggested that internal jugular CVCs are more likely to become infected than are subclavian catheters [81]. However, this issue remains controversial, as other investigators have presented data to the contrary [93]. Another risk factor is the direct application of transparent plastic dressings to the CVC insertion site. Conly and coworkers [47] have shown that this type of dressing leads to a warm, moist insertion site with a high microbial burden, thereby increasing the risk ofcatheter colonization and septicemia. This finding has been supported by those of several other investigations [94, 95]. Other risk factors include frequent manipulations of catheters [20, 21] (as with Swan-Ganz catheters), use ofcontaminated antiseptic skin solutions on the insertion site [48, 49], use of improper insertion and maintenance techniques [96, 97] such as the violation of aseptic techniques by inexperi-

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infusate tubing every 24 hours is no more protective than changing them every 72 hours [115, 116].

Management The treatment and management of catheter-related infections depend on at least four variables: (I) the extent of the infection, that is, whether the infection is local (exit-site or tunnel infection) or systemic (uncomplicated septicemia or septic thrombosis); (2) the microorganisms causing the infection (s. epidermidis, S. aureus, C. albicans. or gram-negative bacilli); (3) the type of catheter (a surgically implantable or percutaneous nontunneled CVC); and (4) the underlying condition of the catheterized host (a patient who is in critical condition or is immunosuppressed or a patient who has a low platelet count or coagulopathy). Prudent decisions about the duration and type ofantimicrobial therapy and the catheter's removal should be made after each case is examined in light of these four variables.

Local Infections Exit-site infections are the least serious infectious complications related to catheters. Benezra and co-workers [76] showed that such infections, except for those caused by Pseudomonas species, could be treated with antibiotics and local care without removal of the tunneled catheter. However, in the case ofan exit-site infection related to a short-term percutaneous CVC, the catheter should be removed when a patient is febrile or septic and fails to respond to intravenous antibiotics. Tunnel infections are often serious and are best managed by removing the CVC and administering intravenous antibiotics [76]. A tunnel infection caused by Mycobacterium fortuitum or Mycobacterium chelonae may require surgical excision of the infected tunnel after catheter removal and the initiation of antibiotics [117].

Systemic Infections Catheter-related septicemia with or without a local infection (exit-site or tunnel infection) can be classified into two categories: uncomplicated and complicated septicemia. Complicated septicemias are those that are associated with septic thrombosis (septic thrombophlebitis) or deep-seated infections. Most catheter-related septicemias are uncomplicated bloodstream infections that respond well to intravenous antibiotic therapy and, if necessary, catheter removal. Should the septicemia persist for >48 hours after removal of the catheter and initiation ofantibiotic therapy, then a complicated intravascular focus such as endocarditis or septic thrombosis should be considered [118]. Under this circumstance, follow-up with echocardiography and a distal venogram ofthe arm are warranted. Septic thrombosis ofthe cen-


Schwartz et al. [103] have used a solution of heparin and vancomycin to flush tunneled CVCs and compared its efficacy with that ofheparin alone. Daily flushing with heparinj vancomycin decreased the frequency of catheter-related bacteremia attributed to luminal colonization with gram-positive organisms that were susceptible to vancomycin. It is unknown whether flushing with heparinjvancomycin will make any difference in the overall rate of catheter-related infections. Investigators have recently studied the protective effect of coating catheters with antibiotics or antiseptics. Kamal and colleagues [104] demonstrated the protective efficacy of bonding CVCs and cefazolin with use of a cationic bonding surfactant (tridodecyl methylammonium chloride). Maki and colleagues [105] coated CVCs with silver sulfadiazine and chlorhexidine; coated CVCs were twofold less likely to become colonized and were at least fourfold less likely to produce bacteremia than were noncoated CVCs (4.7% vs, 1.0%, P =: .02). Insertion of a CVC with use of maximal sterile barriers may help minimize catheter-related infections. A maximal sterile barrier involves wearing sterile gloves, a mask, a gown, and a cap and using a large drape (the normal procedure involves wearing gloves and using a small drape). McCormick and Maki [106] have shown that using maximal sterile barriers led to a fourfold decrease in the rate of pulmonary artery catheter-related bacteremia and a significant decrease in the colonization of the introducer. Further confirmatory data are required to support the cost-effectiveness of such a practice. The role of CVC exchange over a guidewire as a preventive or therapeutic procedure is a controversial issue. The results of several uncontrolled trials in which quantitative cultures were not performed suggested that the routine exchange ofCVCs would reduce the risk ofCVC-related infections [107, 108]. However, Pettigrew and co-workers [109] showed that organisms colonizing a CVC could be transferred to the new CVC during exchange over a guidewire. With use of semiquantitative catheter cultures, Eyer et al. [lIO] showed that the external surface of only 25%ofCVCs became cross-contaminated. In two recent prospective clinical trials [6, Ill], patients were randomized to undergo the exchange of the CVC over a wire every 3 days or the exchange ofthe CVC only when clinically indicated; these studies failed to show any preventive benefit from regularly scheduled exchanges. Lam and co-workers [112] showed that the exchange of the CVC over a guidewire carried with it a high risk of reinfecting the new CVC and of showering the lung with small septic emboli in a sheep model. Other practices have also failed to show any preventive potential. Use of in-line filters, which can reduce the rate of phlebitis, does not decrease the frequency of catheter infections [113, 114]. Changing the insertion site dressing and the




the clinician differentiate between a complicated and uncomplicated course. In a study of 55 patients who were receiving active intravenous antibiotics for catheter-related S. aureus bacteremia, we showed that fever and/or bacteremia persisting for > 3 days after catheter removal strongly suggests a complicated course [129]. Catheter removal is more favored in the case ofS. aureus bacteremia than in the case of bacteremia due to coagulase-negative staphylococci. Dugdale and Ramsey [132] have shown that for patients with Hickman catheter-associated S. aureus bacteremia, retention of the catheter results in a higher rate of relapse and sepsis-related death than that observed when the Hickman catheter is removed. Yeasts. Catheter-related candidemia can be treated with a short course of amphotericin B that consists of 5.0-7.0 mg/kg (0.5 rng/Ikg-d] for 10-14 days). As in cases of S. aureus bacteremia, the physician should limit short-course therapy to uncomplicated cases. A thorough evaluation, including fundoscopic examination, is necessary to rule out retinitis. High-grade candidemia after catheter removal (>2 days ofcandidemia while antifungal therapy is administered) necessitates echocardiography to rule out endocarditis and venography to rule out septic thrombosis of the central vein [118]. Whether catheter removal is necessary in uncomplicated cases remains a controversial issue. Eppes et al. [135] reported retrospective data suggesting that failure to remove the catheter resulted in increased morbidity and mortality as well as prolonged duration of candidemia. Quantitative blood and catheter cultures were not done in this study, and no evidence was included that the reported episodes of candidemia were catheter related. There are no solid data at this point that would compel the clinician to immediately remove a surgically implanted CVC in the setting of catheterrelated candidemia. Pending further prospective data, the clinician should consider removing a CVC when a patient fails to respond to antifungal therapy within 96 hours or when the candidemia persists for >48 hours while the patient is receiving appropriate intravenous antifungal therapy. Gram-negative bacilli. Enteric gram-negative bacilli, such as E. coli and K. pneumoniae, rarely cause catheter-related sepsis. Other bacilli acquired from the hospital environment, such as uou-aeruginosa Pseudomonas species, Acinetobacter species, Achromobacter species, and X. maltophilia, have been associated with catheter-related sepsis. Trimethoprim-sulfamethoxazole is the antibiotic ofchoice in the treatment of X. maltophilia bacteremia, whereas third-generation cephalosporins, carbapenems, monobactams, aminoglycosides, and quinolones could be useful in the treatment of the other gram-negative bacillemias. Duration ofparenteral therapy should not exceed I week. Benezra et al. [76] demonstrated that antibiotic therapy alone does not generally cure catheter-related infections caused by Pseudomonas species; for these infections, the CVC must also be removed. At


tral vein or infective endocarditis should be treated with parenteral antibiotics for at least 4 weeks. The decision to remove a catheter depends on a number of variables, particularly the identification of the causative microbial pathogens. These organisms include coagulase-negative staphylococci, S. aureus. yeasts, gram-negative bacilli, grampositive bacilli, and atypical mycobacteria. Coagulase-negative staphylococci. More than one blood culture positive for the same species, such as S. epidermidis, is required to ascertain the diagnosis ofa true bacteremia and rule out skin contamination [17]. Since most (50%-80%) of the coagulase-negative staphylococci are resistant to the antistaphylococcal penicillins, such as oxacillin, intravenous vancomycin is the treatment ofchoice. The optimal duration of therapy has not yet been defined. However, if the patient responds within 48-72 hours, a course of treatment of 5-7 days should be adequate [21]. Catheter removal was once considered essential [119-121]. However, recent data show that patients with catheter-related bacteremia due to coagulase-negative staphylococci can be treated successfully without catheter removal [15, 16, 76]. In a recent study at M. D. Anderson Cancer Center, we have shown that the rates of acute morbidity and mortality are not influenced by catheter removal. However, if the CVC is not removed, there is a 20% chance that the bacteremia will recur, compared with only a 3% risk of recurrence if the CVC is removed (P < .05) [122]. Therefore, this low, but significant, risk of relapse should enter into the risk-benefit equation in determining whether the CVC should be removed. Although the immediate removal of a surgically implantable CVC that is associated with bacteremia due to coagulase-negative staphylococci might not be possible for a patient with cancer and thrombocytopenia, the CVC should not be left in place any longer than is necessary, particularly following an infection from such a bacterium. S. aureus. Serious infectious complications have been reported in association with catheter-related S. aureus bacteremia. The frequency of such complications ranges from 19% to 31% in the general medical patient population [123-129] and from 33% to 46% among patients with cancer and among other high-risk patients [130-134]. These reported infectious complications consisted of septic thrombosis, fatal sepsis, and deep-seated infections, such as endocarditis, osteomyelitis, septic emboli, and abscesses. It is crucial that the physician differentiates between a complicated case of S. aureus bacteremia and an uncomplicated one. An uncomplicated case should be treated for at least 10 days with intravenous antistaphylococcal antibiotics, either semisynthetic penicillins or vancomycin [129]. However, the duration of therapy should not exceed 2 weeks. For bacteremia complicated by deep-seated infections or septic thrombosis, optimal treatment should consist of at least a 4-week course of intravenous antibiotics [134]. Simple clinical parameters might help

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Conclusions Infection is one ofthe leading complications ofindwelling vascular catheters. The diagnosis of catheter-related septicemia should be considered in the case of staphylococcal or candidal septicemia for which no apparent source except the catheter can be found. Definitive diagnosis requires the performance of either quantitative catheter cultures or differential quantitative blood cultures. Coagulase-negative staphylococci, S. aureus, and Candida species are the most common organisms reported to cause catheter-related infections. The skin and catheter hub are the two major sources of the colonizing organisms. Risk factors predisposing to infections include prolonged catheterization; frequent manipulation of the catheter; improper aseptic insertion and maintenance techniques; poor placement ofthe catheter; the use ofthrombogenic catheter material, transparent plastic dressings, and contaminated skin solutions; and, possibly, the use of multilumen CVCs. Preventive measures against these infections include placement and maintenance of catheters by a skilled infusion-therapy team, coating of catheters with antiseptic agents, and the use of silver-impregnated cuffs (for shortterm CVCs) and topical disinfectants such as chlorhexidine and topical antibiotics. The exchange ofCVCs over a guide-

wire might be useful diagnostically but has not been proven to be of any therapeutic or preventive value. Management depends on several factors, particularly the extent of the infection and the causative organisms. Exit-site infections can be treated with local care and antibiotics without catheter removal. Tunnel infections are more serious and usually require catheter removal and antibiotic treatment. Bacteremia due to coagulase-negative staphylococci can be treated without catheter removal, but there is a slight risk of relapse if the catheter is retained. Catheter-related bacteremia due to S. aureus is associated with a high rate of serious complications. Data suggest that the catheter should be removed and the patient treated for at least 10 days with appropriate intravenous antibiotics. Catheter-related candidemia can be treated with a short course (I 0-14 days) of antifungal therapy; however, the issue of catheter removal remains controversial.

Acknowledgments The authors thank Dr. John W. Costerton and Dr. Ushi Sabharwal for their assistancein the electron microscopicexamination of a colonized catheter.

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CME Test

EXTENSION

This test affords you the opportunity to assess your knowledge and understanding of the material presented in the preceding clinical article "Infectious Complications oflndwelling Vascular Catheters," authored by Issam I. Raad and Gerald P. Bodey, and to earn continuing medic al education (CME) credit. As an organization accredited by ACCME to provide con tinuing medical education, the Department of Continuing Education in Health Sciences. UCLA Extension. certifie s that this CME activity meets the criteria for I hour in Cat egory I of the Physician's Recognition Award of the American Med ical Association and the California Medical Association Certificate in Continuing Medical Education. To earn credit. read the State-of-the-Art Clinical Article carefully and answer the following qu estions. Mark your answer by circling the correct responses on the answer card (usually found toward the front of the issue) and mail after affixing first class postage. To earn credit. a minimum score of 80% mu st be obtained. Certificates of CME credit will be awarded on a per volume (biannual) basis. Each answer card must be submitted within 3 months of the date of issue. Th is program is made possible by an educational grant from Roche Laboratories. I. Which of the following catheters is associated with the highest risk of catheter-related septicemia? A. Peripheral venous catheters B. Peripheral arterial catheters C. Central venous ports D. Noncuffed central venous catheters E. Hickman-Broviac catheters

2. Which of the following is not suggestive of primary septicemia? A. The indwelling catheter is the most likely source. B. The causative organisms are usually Staphylococcus epidermidis and other skin organ isms. C. It is often preceded by no socomial pneumonia. D. It is common among patients in the intensive care unit. E. It is not related to surgical wound or urinary tract infections. 3. Which of the following organisms rarely cause catheterrelated infections? A. Coagulase-negative staphylococci

B. Staphylococcus aureus C. Candida albicans D. Klebsiella pneumoniae E. Xanthomonas malt ophilia 4. T he most likely source for the colonization of indwelling short-term noncuffed central venous catheters is A. The skin around the insertion site. B. Th e catheter hub. C. Contaminated infu sate. D. Hematogenous seeding from another infected site. E. Hematogenous seeding from the gut. 5. All of the following substances would enhance the adherence ofstaphylococcal organisms to catheter surfaces except A. Polyvinylchloride catheter material. B. Fibronectin. C. Albumin . D. Fibrin. E. Fibrous glycocal yx (slime).


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CME Test

D. Increased risk of endocarditis. E. Increased risk of relapse. 9. Catheter-related Staphylococcus aureus bacteremia A. Is rarely «3%) associated with deep-seated infections or septic thrombophlebitis. B. Is successfully treated without removal of the catheter. C. Should always be treated for at least 4 weeks with intravenous antibiotics. D. Is characterized by persistent fever or bacteremia for > 3 days after catheter removal in complicated cases. E. Should always be treated with intravenous vancomycin. 10. Septic thrombosis of the central vein is highly suspected in the case of catheter-related candidemia if A. More than 100 Candida colonies are cultured from a catheter segment. B. Simultaneous quantitative blood cultures reveal at least a 10:1 colony count from the CVC compared with that in blood from the peripheral vein. C. Candidemia persists for >48 hours after catheter removal. D. Insertion site inflammation is noted. E. Urine culture reveals the same Candida species as that isolated from blood.


6. Factors that decrease the risk of catheter-related infections by lowering the microbial burden at the skin insertion site include all of the following except A. Topical polymyxin/neomycin/bacitracin. B. 2%Calcium mupirocin ointment. C. 2% Aqueous chlorhexidine gluconate. D. Dry gauze dressing vs. transparent plastic dressing. E. Frequent dressing changes (every 24 hours). 7. Which of the following factors have been shown.to significantly decrease the rate of catheter-related infections? A. Routine exchange of the catheter over a guidewire every 72 hours B. Frequent dressing changes (every 24 hours) C. In-line filters D. Applying 10% povidone-iodine to the insertion site E. Applying 2% chlorhexidine gluconate to the insertion site 8. Failure to remove the CVC from patients with catheterrelated bacteremia due to coagulase-negative staphylococci is associated with A. High related mortality. B. Persistent bacteremia despite administration of active intravenous antibiotics. C. High rate of relapse (>50%).


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Delayed infectious complications of peritoneal dialysis catheters.

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Experience with indwelling ureteral stent catheters.

Extremity necrosis caused by indwelling arterial catheters.

Letter: Stabiliser for long-term indwelling catheters.

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Comparison of symptom characteristics of indwelling ureteral catheters.

Control of Bacteraemia from Indwelling Central Venous Catheters.

Scanning electron microscopy of bacterial biofilms on indwelling bladder catheters.

Spontaneous migration of long-term indwelling venous catheters.

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Use of percutaneous silastic central venous catheters in neonates and the management of infectious complications.

The effect of right atrial catheters on infectious complications of chemotherapy in children.

Infectious and mechanical complications of central venous catheters placed by percutaneous venipuncture and over guidewires.

Should we really compare indwelling pleural catheters to any pleurodesis?

Patency and Complications of Translumbar Dialysis Catheters.

Central vascular catheters and infections.

[Complications of intravenous therapy with peripheral indwelling catheter].

Microbial colonization of indwelling central venous catheters: statistical evaluation of potential contaminating factors.

Urease-induced precipitation of phosphate salts in vitro on indwelling catheters made of different materials.

Study of the effects of education on patients' knowledge and acceptance of their indwelling urethral catheters.