Original Article

Central Venous Catheter - Related Infections: An Overview with Special Emphasis on Diagnosis, Prevention and Management

S Öncü, S Sakarya

Keywords

central venous catheter, diagnosis, infection, prevention, treatment

Citation

S Öncü, S Sakarya. Central Venous Catheter - Related Infections: An Overview with Special Emphasis on Diagnosis, Prevention and Management. The Internet Journal of Anesthesiology. 2002 Volume 7 Number 1.

Abstract


Backround: The use of intravascular catheters for vascular access and haemodynamic monitoring has become a central part of modern medicine. Although CVCs have significant benefits in many clinical situations, catheter - related infection (CRI) remains a leading cause of nosocomial infections, especially in intensive care units and is associated with significant patient morbidity, mortality, and hospital costs.

There are four potential sources for CRI: the skin insertion site, the catheter hub, hematogenous seeding from a distant infection and contaminated infusate. The key factors for pathogenesis include bacterial adherence, host defence mechanisms and catheter material. Definite diagnosis of CRI necessitates removal of the catheter in most cases. However recenly described techniques may allow diagnosis of CRI without catheter removal. As most CRI originate from skin insertion site and catheter hub successful preventive strategies reduce CRI.

Removal of the catheter in clinical practice for the management of CRI is still recommended in many cases but in specific situations catheter salvage may be undertaken. Regarding antimicrobial therapy, it can be administered either on an empirical basis or after a well-established microbiological diagnosis. Most of the CRI will be treated for a period of 7 to 14 days, depending on the isolated microorganisms.

Conclusion: Infection is one of the leading complications of indwelling central venous catheters. CVC infections are substantial and preventable cause of iatrogenic morbidity and mortality. Therefore the management of CRI, including accurate diagnosis, effective preventive strategies, therapeutic clinical decisions related to catheter removal must be guided by current knowledge.

 

Backround

Central venous catheters (CVCs) are used for the monitoring and therapy of critically ill patients. Estimates of their use in the United States alone suggest that over five million CVCs are inserted annualy 1, 2. Unfortunately, these devices are associated with a number of complications, amongst which infection predominates. CVCs are probably responsible for about 250,000 cases per year of nosocomial bacteremia in the United States, although some estimates are as high as 400,000 cases per year 3, 4. Currently, catheter-related infection (CRI) is a major cause of patient morbidity and mortality, a reason for premature catheter removal and an explanation for the increase in cost and use of resources 5,6,7,8. The appropriate management of CVCs has therefore, become a major challenge for physicians.

Pathogenesis

There are four potential sources for CRI:

  • the skin insertion site

  • the catheter hub

  • hematogenous seeding from a distant infection

  • contaminated infusate

The skin insertion site and the catheter hub are by far the two most important sources. Approximately 65% of CRI originate from the skin flora, 30% from the contaminated hub and 5% from other pathways 9,10,11. For short-term catheters, skin contamination is the most likely mechanism of pathogenesis, whereas for long-term catheters, hub contamination is more frequent3. Skin organisms migrate from the skin insertion site along the external surface of the catheter, colonising the distal intravascular tip of the catheter, and ultimately causing bloodstream infection. Hub contamination is more common in long-term catheters because such catheters often have to be intercepted and manipulated12. Organisms are usually introduced into the hub from the hands of medical personnel. From this contaminated hub, the organisms migrate along the internal surface of the catheter, where they can cause a bloodstream infection13.

The key factors for pathogenesis include bacterial adherence, host defence mechanisms and catheter material14. Host glycoproteins, such as fibrinojen, fibronectin, collagen and laminin, adsorbed on the surface of intravenous devices, form a biofilm layer that enhances bacterial adherence to foreign material, in particular, Staphlococcus aureus and coagulase-negative staphylococci (CNS) 14. Among factors possibly explaining the frequent colonization of catheters by staphylococci, the microbial production of mucoid exopolymeric substances and the presence of receptors to plasma proteins absorbed onto the biomaterial surface have been considered14,15,16. Finally, the material from which the catheter is made is important. The physical characteristics of the catheter, such as surface irregularities and charge difference, facilitate bacterial adherance14. Hydrophobic staphylococcal organisms adhere better to polyvinyl chloride, silicone, and polyethylene surfaces than to polyurethane or Teflon polymers 17, 18.

Definitions

  • Catheter colonization: Growth of ≥ 15 colony forming units (semiquantative culture) or >103 (quantitative culture) from a proximal or distal catheter segment in the absence of accompanying clinical symptoms.

  • Exit-site infection: Erythema, tenderness, induration, or purulence within 2 cm of the skin at the exit site of the catheter.

  • Tunnel infection: Tenderness, erythema, and/or induration >2cm from the catheter exit site, along the subcutaneus tract of a tunneled catheter (e.g., Hickman or Broviac catheter), with or without concomitant bloodstream infection

  • Pocket infection: Infected fluid in the subcutaneus pocket of a totally implanted intrascular device; often associated with tenderness, erythema, and/or induration over the pocket; spontaneus rupture and drainage, or necrosis of the overlying skin, with or without concomitant bloodstream infection, may also occur.

  • Infusate-related bloodstream infection: Concordant growth of the same orgaganism from the infusate and blood cultures with no other identifiable source of infection.

  • Catheter-related bloodstream infection (CRBI): Isolation of the same organism (i.e., identical species, antibiogram) from culture of a catheter segment and from the blood (preferably drawn from a peripheral vein) of a patient with accompanying clinical symptoms of BSI and no other apparent source of infection. In the absence of laboratory confirmation, defervescence after removal of an implicated catheter from a patient with BSI may be considered indirect evidence of CR-BSI.

Microbiology

Most of the micro-organisms implicated in CRIs arise from the skin flora. Staphylococci are the most frequently isolated pathogens in CRI, particularly coagulase negative-staphylococci (CNS), followed by enterococci, S.aureus and Candida species20,21,22. Gram-negative bacilli are usually found at lower frequency and include Pseudomonas spp., Enterobacter spp. and other organisms (Table1). Of these organisms, the ratio of catheter colonization to bloodstream infection was highest for S.aureus followed by C.albicans and then CNS23. This probably reflects the relative virulence of these organisms as pathogens on intravascular devices21. Concomitant with the increasing use of broad-spectrum antimicrobials, cases of CRI caused by a variety of unusual bacterial and fungal pathogens (such as Achromobacter sp., Mycobacterium fortuitum, M.chelonei, Malassezia furfur ) have been reported with increasing frequency 4, 24.

Figure 1
Table 1: Etiology of CRI

Diagnosis

Fever and signs of sepsis, such as chills, rigors, hypotension, hyperventilation should always be considered as CRI when there is no other identifiable source of infection is present. But clinical findings are unreliable for establishing a diagnosis of CRI.

Catheter-associated infections can be considered local or systemic. Local phenomena include simple colonization or true infection that may involve exit site, or tunnel. Local inflammatory signs at the catheter's portal of entry or tunnel have a higly predictive value for infection but it's abcence has a very poor negative value 25. Mechanical and chemical factors may also produce inflamation in the absence of infection. Systemic infections involve infection of the bloodstream. As local signs may be completely absent, clinical diagnosis of CRBI may be diffucult. Therefore, microbiological techniques are necessary to identify CRBI. We will describe the most widespread diagnostic methods used, either non-conservative or conservative.

Semiquantititative culture method is the simplest and most commonly used method, in which the catheter segment is rolled across the surface of an agar plate and colony-forming units (cfu) are counted after overnight incubation26. Its limitation is that it cultures organisms solely from the external surface of the catheter27; intraluminal colonization, which is very important after prolonged and excessive use of the catheter hub, is not evaluated by this technique.

Quantitative culture of the catheter segment requires either flushing the segment with broth, or vortexing, or sonication it in broth, followed by serial dilutions and surface plating on blood agar 21, 28, 29. This technique can isolate organisms from both the internal and external surface of catheters.

The yield of ≥15 cfu from a catheter, by means of semiquantitative culture, or a yield of ≥102 from a catheter, by means of quantitative culture in the absence of signs of infection is considered indicative of catheter colonization. A yield of ≥15 cfu from a catheter by means of semiquantitative culture, or a yield of ≥102 from a catheter, by means of quantitative culture with accompanying signs of local or systemic infection, is indicative of CRI 2.

Gram stain may be helpful for the diagnosis of local infections, but it is significantly less sensitive than are quantitative methods for the diagnosis of CRI30. Another method in which acridine orange staining was used to examine catheter segments was found to be more sensitive and specific than Gram stain method 31.

These culture and direct methods all require catheter removal, which may be problematic in certain patients. Therefore , the techniques described below have been developed to make a microbiological diagnosis possible without removing the catheter.

Quantitative blood culturing techniques have been developed as an alternative for the diagnosis of catheter-related bloodstream infection in patients for whom catheter removal is undesirable because of limited vascular access32, 33. This technique comperes colony counts from peripheral- versus central-line blood culture by various means. A five-to tenfold greater colony count of the same organism from the central-line culture is predictive of catheter related bloodstream infection. Among tunneled catheters, for which the method is most accurate, a quantitative culture of blood from the CVC that yields at least 100cfu/mL may be diagnostic without a companion culture of a peripheral blood sample31,33.

A recently introduced technique: The time to growth of cultures drawn through the catheter and by venipuncture of paired samples34, 35. This method makes use of continuous blood-culture monitoring for positivity and comperes the differential time to positivity for qualitative cultures of blood samples drawn from the catheter and a peripheral vein. In a study of diffrential time to positivity, a definite diagnosis of CRB could be made in 16 of the 17 patients who had a positive result of culture of culture of a blood sample from the CVC at least 2 h earlier than they had a positive result of a peripheral blood culture. This method shows a sensitivity of 94% and specifity of 91% for catheter related bloodstrean infection diagnosis, and can be used for routine clinical practise in most hospitals using automatic devices for blood cultures34.

Another method which preserves catheter in place is the endoluminal brush technique. In this technique a wire brush is used to culture the endoluminal surface in situ, then the blood drawn through the catheter is Gram or acridine orange stained. It has a sensitivity of >90% and specificity of 84%36, 37. However, this method is associated with a risk of transient bacteremia, cardiac arrhtmias and embolization 9.

Risk Factors and Preventive Strategies

Risk factors

Several host factors that predispose for CRI have been identified (Table 2)38. Malignant hematologic disorders and AIDS increase the risk of CRI about four times, but the most important risk factor is neutropenia, with an 11-fold increased risk 39, 40. Other risk factors include prolonged catheterization, frequent manipulations, contaminated skin solutions, improper aseptic techniques during insertion and mainnance, number of catheter lumens and location of catheter 18, 41.

Figure 2
Table 2: Host-Related Risk Factors for CRI

Infusion-therapy team and education

Several medical centers have established an experienced infusion therapy team for the insertion and maintenance of catheters. Establisment of such team have shown unequivocal effectiveness in reducing the incidence of CRI and associated complications and costs 42, 43. Educational programs for clinical staff also result in improved care and reduced site colonization of CVCs 44, 45.

Catheter selection

Teflon or polyurethane catheters have been associated with fewer infectious complications than catheters made of polyvinyl chloride or polyethylene17, 46, 47. Some CVCs have multiple infusion ports and their manipulation could increase infection risk . Therefore CVCs with the minumum number of ports or lumens essential for the management of the patient should be used.

Insertion site

Many factors, including patient-specific issues (pre-existing catheters, local infection, anatomic deformity), relative risk of mechanical complications (bleeding, pneumothorax), as well as the risk of infection enter into decision making regarding insertion site selection. Observational studies using multivariate analysis found that risk for infection was significantly decreased with insertion into the subclavian vein. Therefore, insertion of catheter into the subclavian vein is preferred to reduce the risk for infection. However, this risk must be weighed against noninfectious complications associated with subclavian vein insertion.

Sterile Technique and Hand Hygiene

Good hand hygiene before catheter insertion or maintenance, combined with proper aseptic technique during catheter manipulation, provides protection against infection19. Full-barrier precautions during CVC insertion reduces the incidence of CRI compared with standard precautions 13, 19.

Cutaneus Antisepsis

As previously stated, there is a strong association between the level of colonization of the skin at the insertion site and the rate of subsequent catheter colonization and CRI48. Povidone iodine has been the most widely used antiseptic for cleansing CVC-insertion site49. However in some studies chlorhexidine significantly reduced the incidence of microbial colonization of catheters compered with povidone-iodine50, 51. Based on the existing data chlorhexidine containing antiseptics should be preferred, where approved. But other antiseptics including ticture of iodine, 70% alcohol or povidone iodine can also be used as cutaneus antisepsis 19.

Catheter Dressing

High levels of colonization of the insertion site correlate with increased frequency of catheter colonization and CRI18, 48. Therefore, any dressing over an insertion site that promotes bacterial growth might be presumed to increase infection rates. Steril gauze or sterile, transparent, semipermeable dressings are used to cover the catheter site 52, 53. Transparent dressings reliably secure the device, permit continuous observation of the insertion site, do not become saturated with respiratory or other body fluids, and require less frequent changes than do standard gauze and tape dressings19. The choice of dressing can be a matter of preference. If blood is oozing from the catheter insertion site, gauze dressing might be preferred. The catheter-site dressing should be replaced if the dressing becomes damp, loosened, or visibly soiled. Current CDC guidelines prefer to replace dressings used on short-term CVC sites every 2 days for gauze dressings and at least every 7 days for transparent dressings19.

Duration of Catheters

The practice of routinely changing catheters according to some defined time period to reduce the risk of CRI is referred to as “scheduled” replacement. There is no support from the literature that catheter replacement at sheduled time intervals will reduce the CRI rates54,55,56. Thus, routine replacement of CVCs is not necessary for catheters that are functioning and have no evidence of causing local or systemic complications.

Administration set and fluid changes

Replacing administration sets no more than 72 hours after initiation of use is safe and cost effective. While blood products and lipid emulsions are more likely to sustain bacterial growth, more frequent changes of administration sets are indicated as these products have been identified as independent risk factors for CRI.

Antimicrobial/Antiseptic Impregnated Catheters and Cuffs

Certain CVCs that are coated or impregnated with antimicrobial or antiseptic agents can decrease the risk for CRI19. Use of these catheters might be cost effective in ICU patients, burn patients, neutropenic patients, and other patients populations in which the rate of infection exceeds 3,3 per 1,000 catheters day 3.

Chlorhexidine/Silver sulfadiazine

Two meta-analyses demonstrated that CVCs coated with chlorhexidine/silver sulfadiazine reduced the risk for CRI compared with noncoated catheters57, 58. As the antimicrobial activity is waining over time , these catheters should be considered when the expected duration of catheterization is less than 2 weeks, particularly if there is a high rate of infection despite adherence to other strategies.

Minocycline/Rifampin

The duration of antimicrobial activity of CVCs impregnated with minocycline/rifampin is longer than that of the chlorhexidine/silver sulfadiazine coated catheters 59. In a multicenter randomized trial, these CVCs were associated with lower rates of CRI than chlorhexidine-silver sulfadiazine impregnated catheters 59.

Platinium/Silver

Platinium/Silver impregnated CVCs and silver cuffs attached to CVCs are other available catheters to prevent CRI but futher studies are needed to show their effectiveness in reducing CRI incidence19.

Management

Once the diagnosis of CRI is established or suspected, prudent decisions about the duration, type of antimicrobial therapy and the catheter's removal should be made dependent on different factors concerning the patient, the pathogen, and the catheter itself. Removal of an catheter suspected to be infected is recommended. However, there are circumstances in which removal of the catheter is diffucult or not desirable unless absolutely necessary. This is the case in patients with poor venous access, in patients for whom trying a new catheterization involves high risk (e.g bleeding diatesis) and with catheters that are surgically implanted. In hemodynamically stable patients, if no signs of metastatic infection and tunnel or port infection is present salvage of the catheter can be undertaken in case the blood gets sterile in 48-72 hours after antibiotic initiation 9. CRI caused by CNS may be succesfully managed with the catheter in situ2. Although catheter retention is associated with higher risk of the bacteremia, mortality and morbidity are not influenced by catheter removal 60. Therefore, catheter retention might be considered in patients with CRI due to CNS, provided that there is no indication for catheter removal (Table 3 ). Nonetheless, there is a 20% risk of bacteremia recurrence if the catheter remains in place, especially for longer than 3 weeks after initial bacteremia episode61.

Figure 3
Table 3: Indications for catheter removal

Regarding antimicrobial therapy, it can be administered either on an empirical basis or after a well-established microbiological diagnosis. Although removal of the catheter alone may result in clinical cure in selected cases, it is generally recommended to treat CRI systemically with appropriate antibiotics2, 62. Most of the CRI will be treated for a period of 7 to 14 days, depending on the isolated microorganisms2,9,60. However, in cases of complicated CRI, the vascular catheter should be removed and the infection treated with antibiotics for at least 4 weeks 2,39,60.

Coagulase-negative staphylococci

Most patients have a benign clinical course, but rarely do patients develop frank sepsis with a poor outcome63,64,65. A 5-7 day course of antimicrobials should be adequate if the patient responds within 48 to 72 hours2. Patients responding antibiotic therapy after 72h and in patiens the catheter is retained in place should have a 14-day course of antibiotics therapy 2,9.

S.aureus

The catheter must definetely be removed; otherwise serious infectious complications may arise. Also failure to remove the catheter is associated with persistent bacteremia, relapses, and increased mortality66, 67. Uncomplicated episodes of S.aureus infections should be treated with appropriate antibiotics given intravenously for at laest 2 weeks2. However, in cases of complicated infections or in patients with prolonged fever under appropriate antimicrobial therapy, much longer periods are needed2.

Gram-positive bacilli

Removal of the catheter has been recommended for the succesful management of such infections. Treatment should be prescribed on the basis of susceptibility tests60.

Gram-negative bacilli

Gram – negative bacilli such as Pseudomonas aeruginosa, Acinetobacter spp., E.coli, Klebsiella spp. are also relatively common causes of CRIs. Removal of the catheter is important, as failure to remove it results in significantly higher rates of treatment failure and recurrence of bacteremia2,18. Catheter removal and a 10-14 day course of antimicrobial is recommended2,60.

Candida spp.

Removal of the CVC is clearly necessary in candida associated CRI2, 68, 69. Catheter retention is an independent risk factor for the persistance of candidemia and higher mortality rate68,69 .Antifungal therapy should be started in all cases. Intravenous fluconazole is the drug of choice for CRI due to Candida spp.2. In the cases caused by candida spp. not susceptible to fluconazole, treatment has to be changed to amphotericin B70, 71. Therapy with antifungal agent is recommended for 14 days after last positive blood culture.

Atypical mycobacteria

M.fortuitum and M.chelonea, have been shown to cause CRI. Catheter removal is crucial for the succesful management of CRI due to these organisms. Combination of cefoxitin and amikacin is the best coverage for the treatment18.

Antibiotic Lock Therapy

The antibiotic-lock technique consist of instillation the catheter lumen with an antibiotic solution over a period of 12-24 h in order to sterilize the catheter 72,73,74,75. It has been demonstrated to be effective in eliminating CRB in several studies73,74,75. With this method, a high local concentration of an appropriate antibiotic can be applied in the catheter lumen while avoiding systemic toxicity and the monitor serum drug levels. This technique is particularly appealing for treatment of noncomplicated CRI of intraluminal origin76. Although the duration of antibiotic lock therapy has varied among different studies, it most often is 2 weeks2,76.

Correspondence to

Serkan ÖNCÜ Adnan Menderes University, Medical Faculty, Department of Infectious Diseases and Clinical Microbiology 09100 Aydin – TURKEY e-mail: serkanoncu@hotmail.com Phone: +90.533. 446 82 50 Fax: +90.256. 2120146

References

1. Pearson ML. Guideline for prevention of intravascular device-related infections. Part I. Intravascular device-related infections: an overview. The Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1996; 24:262-77.
2. Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001; 32:1249-72.
3. Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial. Ann Intern Med 1997; 127:257-66.
4. Raad I. Intravascular-catheter-related infections. Lancet 1998; 351:893-8.
5. Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality. Jama 1994; 271:1598-601.
6. Pittet D, Wenzel RP. Nosocomial bloodstream infections. Secular trends in rates, mortality, and contribution to total hospital deaths. Arch Intern Med 1995; 155:1177-84.
7. Dimick JB, Pelz RK, Consunji R, Swoboda SM, Hendrix CW, Lipsett PA. Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit. Arch Surg 2001; 136:229-34.
8. Jarvis WR. Selected aspects of the socioeconomic impact of nosocomial infections: morbidity, mortality, cost, and prevention. Infect Control Hosp Epidemiol 1996; 17:552-7.
9. Bouza E, Burillo A, Munoz P. Catheter-related infections: diagnosis and intravascular treatment. Clin Microbiol Infect 2002; 8:265-74.
10. Sitges-Serra A, Pi-Suner T, Garces JM, Segura M. Pathogenesis and prevention of catheter-related septicemia. Am J Infect Control 1995; 23:310-6.
11. Reed CR, Sessler CN, Glauser FL, Phelan BA. Central venous catheter infections: concepts and controversies. Intensive Care Med 1995; 21:177-83.
12. Linares J, Sitges-Serra A, Garau J, Perez JL, Martin R. Pathogenesis of catheter sepsis: a prospective study with quantitative and semiquantitative cultures of catheter hub and segments. J Clin Microbiol 1985; 21:357-60.
13. 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; 15:231-8.
14. Pascual A. Pathogenesis of catheter-related infections: lessons for new designs. Clin Microbiol Infect 2002; 8:256-64.
15. Ammendolia MG, Di Rosa R, Montanaro L, Arciola CR, Baldassarri L. Slime production and expression of the slime-associated antigen by staphylococcal clinical isolates. J Clin Microbiol 1999; 37:3235-8.
16. Eggimann P, Pittet D. Overview of catheter-related infections with special emphasis on prevention based on educational programs. Clin Microbiol Infect 2002; 8:295-309.
17. Sheth NK, Franson TR, Rose HD, Buckmire FL, Cooper JA, Sohnle PG. Colonization of bacteria on polyvinyl chloride and Teflon intravascular catheters in hospitalized patients. J Clin Microbiol 1983; 18:1061-3.
18. Raad, II, Bodey GP. Infectious complications of indwelling vascular catheters. Clin Infect Dis 1992; 15:197-208.
19. O'Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention. MMWR Recomm Rep 2002; 51:1-29.
20. Haslett TM, Isenberg HD, Hilton E, Tucci V, Kay BG, Vellozzi EM. Microbiology of indwelling central intravascular catheters. J Clin Microbiol 1988; 26:696-701.
21. Sherertz RJ, Raad, II, Belani A, et al. Three-year experience with sonicated vascular catheter cultures in a clinical microbiology laboratory. J Clin Microbiol 1990; 28:76-82.
22. Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999; 29:239-44.
23. Crump JA, Collignon PJ. Intravascular catheter-associated infections. Eur J Clin Microbiol Infect Dis 2000; 19:1-8.
24. Kiehn TE, Armstrong D. Changes in the spectrum of organisms causing bacteremia and fungemia in immunocompromised patients due to venous access devices. Eur J Clin Microbiol Infect Dis 1990; 9:869-72.
25. Collignon PJ. Intravascular catheter associated sepsis: a common problem. The Australian Study on Intravascular Catheter Associated Sepsis. Med J Aust 1994; 161:374-8.
26. Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method for identifying intravenous-catheter-related infection. N Engl J Med 1977; 296:1305-9.
27. Hampton AA, Sherertz RJ. Vascular-access infections in hospitalized patients. Surg Clin North Am 1988; 68:57-71.
28. Brun-Buisson C, Abrouk F, Legrand P, Huet Y, Larabi S, Rapin M. Diagnosis of central venous catheter-related sepsis. Critical level of quantitative tip cultures. Arch Intern Med 1987; 147:873-7.
29. Cleri DJ, Corrado ML, Seligman SJ. Quantitative culture of intravenous catheters and other intravascular inserts. J Infect Dis 1980; 141:781-6.
30. Cooper GL, Hopkins CC. Rapid diagnosis of intravascular catheter-associated infection by direct Gram staining of catheter segments. N Engl J Med 1985; 312:1142-7.
31. Kite P, Dobbins BM, Wilcox MH, McMahon MJ. Rapid diagnosis of central-venous-catheter-related bloodstream infection without catheter removal. Lancet 1999; 354:1504-7.
32. Fan ST, Teoh-Chan CH, Lau KF. Evaluation of central venous catheter sepsis by differential quantitative blood culture. Eur J Clin Microbiol Infect Dis 1989; 8:142-4.
33. Capdevila JA, Planes AM, Palomar M, et al. Value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis. Eur J Clin Microbiol Infect Dis 1992; 11:403-7.
34. Blot F, Schmidt E, Nitenberg G, et al. Earlier positivity of central-venous- versus peripheral-blood cultures is highly predictive of catheter-related sepsis. J Clin Microbiol 1998; 36:105-9.
35. Blot F, Nitenberg G, Chachaty E, et al. Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet 1999; 354:1071-7.
36. Kite P, Dobbins BM, Wilcox MH, et al. Evaluation of a novel endoluminal brush method for in situ diagnosis of catheter related sepsis. J Clin Pathol 1997; 50:278-82.
37. Tighe MJ, Kite P, Thomas D, Fawley WN, McMahon MJ. Rapid diagnosis of catheter-related sepsis using the acridine orange leukocyte cytospin test and an endoluminal brush. JPEN J Parenter Enteral Nutr 1996; 20:215-8.
38. DK H. Infections due to percutaneus intravascular devices. In: Mandell G BJ, Dolin R, ed. Principles and Practice of Infectious Diseases. Vol. 2. Philadelphia: Churchill Livingtone, 2000:3005-3028.
39. Fatkenheuer G, Cornely O, Seifert H. Clinical management of catheter-related infections. Clin Microbiol Infect 2002; 8:545-50.
40. Nouwen JL, Wielenga JJ, van Overhagen H, et al. Hickman catheter-related infections in neutropenic patients: insertion in the operating theater versus insertion in the radiology suite. J Clin Oncol 1999; 17:1304.
41. Mermel LA, Maki DG. Infectious complications of Swan-Ganz pulmonary artery catheters. Pathogenesis, epidemiology, prevention, and management. Am J Respir Crit Care Med 1994; 149:1020-36.
42. Nehme AE. Nutritional support of the hospitalized patient. The team concept. Jama 1980; 243:1906-8.
43. Tomford JW, Hershey CO. The i.v. therapy team: impact on patient care and costs of hospitalization. Nita 1985; 8:387-9.
44. Parras F, Ena J, Bouza E, et al. Impact of an educational program for the prevention of colonization of intravascular catheters. Infect Control Hosp Epidemiol 1994; 15:239-42.
45. Sherertz RJ, Ely EW, Westbrook DM, et al. Education of physicians-in-training can decrease the risk for vascular catheter infection. Ann Intern Med 2000; 132:641-8.
46. 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; 258:2396-403.
47. Maki DG, Ringer M. Risk factors for infusion-related phlebitis with small peripheral venous catheters. A randomized controlled trial. Ann Intern Med 1991; 114:845-54.
48. DG M. Infections caused by intravascular devices used for infusion theraphy: pathogenesis, prevention, and management. In: Bisno AL WF, ed. Infections associated with medical devices. Washington DC: ASM Press, 1994:155-205.
49. Clemence MA, Walker D, Farr BM. Central venous catheter practices: results of a survey. Am J Infect Control 1995; 23:5-12.
50. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991; 338:339-43.
51. Mimoz O, Pieroni L, Lawrence C, et al. Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients. Crit Care Med 1996; 24:1818-23.
52. Maki DG, Stolz SS, Wheeler S, 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; 22:1729-37.
53. Bijma R, Girbes AR, Kleijer DJ, Zwaveling JH. Preventing central venous catheter-related infection in a surgical intensive-care unit. Infect Control Hosp Epidemiol 1999; 20:618-20.
54. Eyer S, Brummitt C, Crossley K, Siegel R, Cerra F. Catheter-related sepsis: prospective, randomized study of three methods of long-term catheter maintenance. Crit Care Med 1990; 18:1073-9.
55. Uldall PR, Merchant N, Woods F, Yarworski U, Vas S. Changing subclavian haemodialysis cannulas to reduce infection. Lancet 1981; 1:1373.
56. Cook D, Randolph A, Kernerman P, et al. Central venous catheter replacement strategies: a systematic review of the literature. Crit Care Med 1997; 25:1417-24.
57. Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med 2000; 132:391-402.
58. Veenstra DL, Saint S, Saha S, Lumley T, Sullivan SD. Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis. Jama 1999; 281:261-7.
59. Darouiche RO, Raad, II, Heard SO, et al. A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group. N Engl J Med 1999; 340:1-8.
60. Afif C RI. Intravascular catheter-related infections. In: D S, ed. Current Therapy of Infectious Diseases. St.Louis: Mosby, 2001:416-418.
61. Raad I, Davis S, Khan A, Tarrand J, Elting L, Bodey GP. Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bacteremia. Infect Control Hosp Epidemiol 1992; 13:215-21.
62. Paiva JA, Pereira JM. Treatment of the afebrile patient after catheter withdrawal: drugs and duration. Clin Microbiol Infect 2002; 8:290-4.
63. Engelhard D, Elishoov H, Strauss N, et al. Nosocomial coagulase-negative staphylococcal infections in bone marrow transplantation recipients with central vein catheter. A 5-year prospective study. Transplantation 1996; 61:430-4.
64. Christensen GD, Bisno AL, Parisi JT, McLaughlin B, Hester MG, Luther RW. Nosocomial septicemia due to multiply antibiotic-resistant Staphylococcus epidermidis. Ann Intern Med 1982; 96:1-10.
65. Sattler FR, Foderaro JB, Aber RC. Staphylococcus epidermidis bacteremia associated with vascular catheters: an important cause of febrile morbidity in hospitalized patients. Infect Control 1984; 5:279-83.
66. Raad, II, Sabbagh MF. Optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia: a study of 55 cases and review. Clin Infect Dis 1992; 14:75-82.
67. Dugdale DC, Ramsey PG. Staphylococcus aureus bacteremia in patients with Hickman catheters. Am J Med 1990; 89:137-41.
68. Eppes SC, Troutman JL, Gutman LT. Outcome of treatment of candidemia in children whose central catheters were removed or retained. Pediatr Infect Dis J 1989; 8:99-104.
69. Dato VM, Dajani AS. Candidemia in children with central venous catheters: role of catheter removal and amphotericin B therapy. Pediatr Infect Dis J 1990; 9:309-14.
70. 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. Candidemia Study Group and the National Institute. N Engl J Med 1994; 331:1325-30.
71. Anaissie EJ, Darouiche RO, Abi-Said D, et al. Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis 1996; 23:964-72.
72. Messing B, Peitra-Cohen S, Debure A, Beliah M, Bernier JJ. Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients. JPEN J Parenter Enteral Nutr 1988; 12:185-9.
73. Benoit JL, Carandang G, Sitrin M, Arnow PM. Intraluminal antibiotic treatment of central venous catheter infections in patients receiving parenteral nutrition at home. Clin Infect Dis 1995; 21:1286-8.
74. Capdevila JA, Segarra A, Planes AM, et al. Successful treatment of haemodialysis catheter-related sepsis without catheter removal. Nephrol Dial Transplant 1993; 8:231-4.
75. Andris DA, Krzywda EA, Edmiston CE, Krepel CJ, Gohr CM. Elimination of intraluminal colonization by antibiotic lock in silicone vascular catheters. Nutrition 1998; 14:427-32.
76. Carratala J. The antibiotic-lock technique for therapy of 'highly needed' infected catheters. Clin Microbiol Infect 2002; 8:282-9.

Author Information

Serkan Öncü, MD
Assistant Professor, Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes University Faculty of Medicine

Serhan Sakarya, MD
Assistant Professor, Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes University Faculty of Medicine

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