Catheter-related bloodstream infections (CRBIs) are a cause of significant morbidity and mortality in intensive care unit patients. Development of CRBIs may occur by several mechanisms. The role of fibrin and biofilm development and their impact on therapy are described. Multiple preventative strategies related to the insertion and maintenance of the catheter site have been identified. Topical antisepsis and use of antibiotic-impregnated catheters are also beneficial for reducing the incidence of CRBI. Antibiotic lock solutionsmay be effective in preventing CRBI for select patients with longterm catheter use. Treatment of CRBIs should be based on suspected organisms, whichmost commonly include staphylococci, gram-negatives, including Pseudomonas aeruginosa andCandida species. Duration of treatment and decisions regarding catheter removal are controversial. Evaluation and treatment of potential complications of CRBIs, including endocarditis, infected thrombophlebitis, osteomyelitis, and endophthalmitis, are essential.
Raad I, Darouiche R.Prevention of infections associated with intravascular devices. Crit Care Med. 1996;2:361-365.
3.
Saint S, Savel RH, Matthay MA. Enhancing the safety of critically ill patients by reducing urinary and central venous catheterrelated infections. Am J Respir Crit Care Med. 2002;165:1475-1479.
4.
Richards M, Edwards J, Culver D, Gaynes R.Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med. 1999;27:887-892.
5.
O'Grady NP, Alexander M, Dellinger P, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2002;35:1281-1307.
6.
Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med. 2000;132:391-402.
7.
Bouza E, Burillo A, Munoz P.Catheter-related infections: diagnosis and intravascular treatment. Clin Microbiol Infect. 2002;8:265-274.
8.
Mehall JR, SaltzmanDA, JacksonRJ, Smith SD. Fibrin sheath enhances central venous catheter infection. Crit Care Med. 2002;30:908-912.
9.
DaveyME, O'Toole GA. Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev. 2000;64:847-867.
10.
Douglas LJ. Candidabiofilms and their role in infection. Trends Microbiol. 2003;11:30-36.
Stickler DJ. Susceptibility of antibiotic-resistant gram-negative bacteria to biocides: a perspective from the study of catheter biofilms. J Appl Microbiol. 2002;92:1635-1705.
13.
Donlan RM. Biofilms: microbial life on surfaces. Emerg Infect Dis. 2002;8:1-19.
14.
Lewis K.Riddle of biofilm resistance. Antimicrob Agents Chemother. 2001;45:999-1007
15.
Watnick P, Kolter R.Biofilm, city of microbes. J Bacteriol. 2000;182:2675-2679.
16.
Schwartz C, Henrickson KJ, Roghmann K, Powell K.Prevention of bacteremia attributed to luminal colonization of tunneled central venous catheters with vancomycin-susceptible organisms. J Clin Oncol. 1990;8:1591-1597.
17.
Lane RK, Matthay MA. Central line infections. Curr Opin Crit Care. 2002;8:441-448.
18.
National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1990-May 1999. Am J Infect Control. 1999;27:520-532.
19.
National Nosocomial Infections Sureveillance (NNIS) System report, data summary from January 1992 through June 2003. Am J Infect Control. 2003;31:481-498.
20.
Pfaller MA, Jones RN, Doern HS, et al. Bloodstream infection due to Candidaspecies: SENTRY antimicrobial surveillance program in North America and Latin America, 1997-1998. Antimicrob Agents Chemother. 2000;44:747-751.
21.
Wey SB, MoriM, PfallerMA, Woolson RF, Wenzel RP. Hospitalacquired candidemia: the attributable mortality and excess length of stay. Arch Intern Med. 1988;148:2642-2645.
22.
Raad II, Hanna HA, Darouchie RO. Diagnosis of catheter-related blood stream infections: is it necessary to culture the subcutaneous catheter segment?Eur J Clin Microbiol Infect Dis. 2001;20:566-568.
23.
Brun-Buisson C, Abrouk F, Legrand P, et al. Diagnosis of central venous catheter-related sepsis: critical levels of quantitative tip cultures. Arch Intern Med. 1987;147:873-877.
24.
Blot F, Schmidt E, NitenbergG, et al. Earlier positivity of centralvenous-versus peripheral blood cultures is highly predictive of catheter-related sepsis. J Clin Microbiol. 1998;36:105-109.
25.
Blot F, Nitenberg G, Chachaty E, et al. Diagnosis of catheterrelated bacteremia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet. 1999;354:1071-1077.
26.
Worthington T, Lambert PA, TraubeA, Elliott TS. Arapid ELISA for the diagnosis of intravascular catheter related sepsis caused by coagulase negative staphylococci. J Clin Pathol. 2002;55:41-43.
27.
Kite P, DobbinsBM, WilcoxMH, McMahonMJ. Rapid diagnosis of central-venous-catheter-related bloodstream infection without catheter removal. Lancet. 1999;354:1504-1507.
28.
Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for themanagement of intravascular catheter-related infections. Clin Infect Dis. 2001;32:1249-1272.
29.
MakiDG. YesVirginia, aseptic technique is very important: maximal barrier precautions during insertion reduce the risk of central venous catheter-related bacteremia. Infect Control Hosp Epidemiol. 1994;15:227-230.
30.
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.
31.
GoetzAM, WagenerMM, Millier JM, Muder RR. Risk of infection due to central venous catheters: effect of site of placement and catheter type. Infect Control Hosp Epidemiol. 1998;19:842-845.
32.
Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA. 2001;286:700-707.
33.
Ruesch S, Walder B, Tramèr MR. Complications of central venous catheters: internal jugular versus subclavian access—a systematic review. Crit Care Med. 2002;30:454-460.
34.
Faubion WC, Wesley JR, Khalidi N, Silva J.Total parenteral nutrition catheter sepsis: impact of the team approach. JPEN J Parenter Enteral Nutr. 1986;10:642-645.
35.
GilliesD, O'Riordan L, WallenM, RankinK, MorrisonA, Nagy S.Timing of intravenous administration set changes: a systematic review. Infect Control Hosp Epidemiol. 2004;25:240-250.
36.
CookD, RandolphA, Kernerman P, et al. Central venous catheter replacement strategies: a systematic review of the literature. Crit Care Med. 1997;25:1417-1424.
37.
Eggimann P, Pittet D.Infection control in the ICU. Chest. 2001;120:2059-2093.
38.
Maki D, Ringer M, Alvarado C.Prospective randomized trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet. 1991;338:339-343.
39.
Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S.Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta analysis. Ann Intern Med. 2002;136:792-801.
40.
Assadian O.Skin antiseptic in reducing the risk of central venous catheter-related infections. Crit Care Med. 2004;32:887-888.
41.
Parienti JJ, du Cheyron D, RamakersM, et al. Alcohol povidoneiodine to prevent central venous catheter colonization: a randomized unit-crossover study. Crit CareMed. 2004;32:708-713.
42.
Ebo DG, StevensWJ, Bridts CH, Matthieu L.Contact allergic dermatitis and life-threatening anaphylaxis to chlorhexidine. J Allergy Clin Immunol. 1998;101:128-129.
43.
Le Pabic F, Sainte-Laudy J, Blanchard N, Moneret-Vautrin DA. First case of anaphylaxis to iodinated povidone. Allergy. 2003;58:826-827.
44.
Torricelli R, Wüthrich B.Life-threatening anaphylactic shock due to skin application of chlorhexidine. Clin Exp Allergy. 1996;26:112-112.
45.
Sesso R, Barbosa D, Leme IL, et al. Staphylococcus aureus prophylaxis in hemodialysis patients using central venous catheter: effect of mupirocin ointment. J Am Soc Nephrol. 1998;9:1085-1092.
46.
Riu S, Ruiz CG, Martinez-Vea A, Peralta C, Oliver JA. Spontaneous rupture of polyurethane peritoneal catheter: a possible deleterious effect of mupirocin ointment. Nephrol Dial Transplant. 1998;13:1870-1871.
47.
Zakrzewska-Bode A, Muytjens HL, Liem KD, Hoogkamp-Korstanje JA. Mupirocin resistance in coagulase-negative staphylococci, after topical prophylaxis for the reduction of colonization of central venous catheters. JHosp Infect. 1995;31:189-193.
48.
Flowers RH III, Schwenzer KJ, Kopel RF, Fisch MJ, Tucker SI, Farr BM. Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter-related infection: a randomized, controlled trial. JAMA. 1989;261:878-883.
49.
Bock SN, Lee RE, Fisher B, et al. A prospective randomized trial evaluating prophylactic antibiotics to prevent triple-lumen catheter-related sepsis in patients treated with immunotherapy. J Clin Oncol. 1990;8:161-169.
50.
Raad II, Hachem RY, Abi-Said D, et al. A prospective crossover randomized trial of novobiocin and rifampin prophylaxis for the prevention of intravascular catheter infections in cancer patients treated with interleukin-2. Cancer. 1998;82:403-411.
51.
McKee R, Dunsmuir R, Whitby M, Garden OJ. Does antibiotic prophylaxis at the time of catheter insertion reduce the incidence of catheter-related sepsis in intravenous nutrition?J Hosp Infect. 1985;6:419-425.
52.
RansonMR, Opperheim BA, Jackson A, Kanthan AF, Scarffe JH. Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients. J Hosp Infect. 1990;15:95-102.
53.
Centers for Disease Control and Prevention. Recommendations for preventing the spread of vancomycin resistance. Recommendations of the Hospital Infections Control Practices Advisory Committee (HICPAC). MMWR Morb Mortal Wkly Rep. 1995;44(RR-12):1-20.
54.
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;281:261-267.
55.
Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. Ann Intern Med. 1997;127:267-274.
56.
Hanna H, BenjaminR, Chatzinikolaou I, et al. Long-termsilicone central venous catheters impregnated with minocycline and rifampin decrease rates of catheter-related bloodstream infection in cancer patients: a prospective randomized clinical trial. J Clin Oncol. 2004;22:3163-3171.
57.
Shorr AF, Humphreys CW, Helman DL. New choice for central venous catheters: potential financial implications. Chest. 2003;124:275-284.
58.
Bassetti S, D'AgostinoR, Sherertz R. Prolonged antimicrobial activity of a catheter containing chlorhexidine-silver sulfadiazine extends protection against catheter infections in vivo. Antimicrob Agents Chemother. 2001;45:1535-1538.
59.
Stephens R, Mythen M, Kallis P, Davies DW, EgnerW, Rickards A.Two episodes of life-threatening anaphylaxis in the same patient to a chlorhexidine-sulphadiazine-coated central venous catheter. Br J Anaesth. 2001;87:306-308.
60.
Walder B, Pittet D, TramerMR. Prevention of bloodstream infections with central venous catheters treated with anti-infective agents depends on catheter type and insertion time: evidence from a meta-analysis. Infect Control Hosp Epidemiol. 2002;23:748-756.
61.
Hanna HA, Raad II, Hackett B, et al. Antibiotic-impregnated catheters associatedwith significant decrease in nosocomial and multidrug-resistant bacteremias in critically ill patients. Chest. 2003;124:1030-1038.
62.
Allon M.Prophylaxis against dialysis catheter-related bacteremia with a novel antimicrobial lock solution. Clin Infect Dis. 2003;36:1539-1544.
63.
Carratala J, Niubo J, Fernandez-Sevilla A, et al. Randomized, double-blind trial of an antibiotic-lock-technique for prevention of gram-positive central venous catheter-related infection in neutropenic patientswith cancer. AntimicrobAgents Chemother. 1999;43:2200-2204.
64.
Henrickson KJ, Axtell RA, Hoover SM, et al. Prevention of central venous catheter-related infections and thrombotic events in immunocompromised children by the use of vancomycin/ ciprofloxacin/heparin flush solution: a randomized, multicenter, double-blind trial. J Clin Oncol. 2000;18:1269-1278.
65.
Daghistani D, Horn M, Rodriguez Z, Schoenike S, Toledano S.Prevention of indwelling central venous catheter sepsis. Med Pediatr Oncol. 1996;26:405-408.
66.
Chatzinikolaou I, Zipf TF, Hanna H, et al. Minocyclineethyenediaminetetraacetate lock solution for the prevention of implantable port infections in children with cancer. Clin Infect Dis. 2003;36:116-119.
67.
Jurewitsh B, Lee T, Park J, Jeejeebhoy K.Taurolodine 2% as an antimicrobial lock solution for prevention of recurrent catheterrelated bloodstream infections. JPEN J Parenter Enteral Nutr. 1998;22:242-244.
68.
Metcalf SC, Chambers ST, PithieAD. Use of ethanol locks to prevent recurrent central line sepsis. J Infect. 2004;49:20-22.
69.
Ranucci M, Isgro G, Giomarelli PP, et al. Impact of oligon central venous catheters on catheter colonization and catheter-related bloodstream infection. Crit Care Med. 2003;31:52-59.
70.
LiuWK, Brown MR, Elliott TS. Mechanisms of the bactericidal activity of low amperage electric current (DC). J Antimicrob Chemother. 1997;39:687-695.
71.
Alem MA, Douglas LJ. Effects of aspirin and other nonsteroidal anti-inflammatory drugs on biofilms and planktonic cells of Candida albicans. Antimicrob Agents Chemother. 2004;48:41-47.
72.
Shinefield H, Black S, Fatten A, et al. Use of Staphylococcus aureusconjugate vaccine in patients receiving hemodialysis. N Engl J Med. 2002;346:491-496.
73.
Jernigan JA, Farr B.Short-course therapy of catheter-associated Staphylococcus aureusbacteremia: a meta-analysis. Ann Intern Med. 1993;119:304-311.
74.
Fowler VG, Li J, Corey GR, et al. Role of echocardiography in evaluation of patients with Staphylococcus aureusbacteremia: experience in 103 patients. J Am Coll Cardiol. 1997;30:1072-1078.
75.
Herrmann M, Peters G.Catheter-associated infections caused by coagulase-negative staphylococci: clinical and biological aspects. In: Seifert H, Jansen B, Farr BM, eds. Catheter-Related Infections. New York, NY: Marcel Dekker; 1997:79-109.
76.
Messing B, Man F, Colimon R, et al. Antibiotic lock technique is an effective treatment of bacterial catheter related sepsis during parenteral nutrition. Clin Nutr. 1990;9:220-227.
77.
Krzywda EA, Andris DA, Edmiston CE, et al. Treatment of Hickman catheter sepsis using antibiotic lock in silicone vascular catheters. Nutrition. 1998;14:427-432.
78.
Johnson DC, Johnson FL, Goldman S.Preliminary results treating persistent central venous catheter infectionswith the antibiotic lock technique in pediatric patients. Pediatr Infect Dis J. 1994;13:930-931.
79.
Anthony TU, Rubin LG. Stability of antibiotics used for antibioticlock treatment of infections of implantable venous devices (ports). Antimicrob Agents Chemother. 1999;43:2074-2076.
80.
Droste JC, Jeraj HA, MacDonaldA, Farrington K.Stability and in vitro efficacy of antibiotic-heparin lock solutions potentially useful for treatment of central venous catheter-related sepsis. J Antimicrob Chemother. 2003;51:849-855.
81.
Ascher DP, Shoupe BA, Maybee D, et al. Persistent catheterrelated bacteremia: clearance with antibiotics and urokinase. J Pediatr Surg. 1993;28:627-629.
82.
Fishbein JD, Friedman HS, Bennett BBH, et al. Catheter-related sepsis refractory to antibiotics treated successfully with adjunctive urokinase infusion. Pediatr Infect Dis J. 1990;9:676-678.
83.
JonesGR, Konsler GK, DunawayRP, et al. Prospective analysis of urokinase in treatment of catheter sepsis in pediatric hematologyoncology patients. J Clin Oncol. 1993;28:350-357.
84.
Atkinson JB, Chamberlin K, Boody BA. A prospective randomized trial of urokinase as an adjuvant in the treatment of proven Hickman catheter-sepsis. J Pediatr Surg. 1998;33:714-716.
85.
La Quaglia MP, Caldwell C, Lucas A, et al. A prospective randomized double-blind trial of bolus urokinase in the treatment of established Hickman catheter sepsis in children. J Pediatr Surg. 1994;29:742-745.
86.
Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38:161-189.
87.
Mora-Duarte J, Betts R, Rotstein R, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347:2020-2029.
88.
Anaisse EJ, Rex JH, Uzun Ö, Vartivarian S.Predictors of adverse outcome in cancer patients with candidemia. Am J Med. 1998;104:238-245.
89.
Nguyen MH, Peacock JE, Tanner DC, et al. Therapeutic approaches in patients with candidemia: evaluation in a multicenter, prospective, observational study. Arch Intern Med. 1995;155:2429-2435.
90.
Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. 2003;37:634-643.
91.
Johnson MD, MacDougall C, Ostrosky-Zeichner Perfect JR, Rex JH. Combination antifungal therapy. Antimicrob Agents Chemother. 2004;48:693-715.
92.
Rex JH, Pappas PG, Karchmer AW, et al. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic patients. Clin Infect Dis. 2003;36:1221-1228.
93.
Food and Drug Administration. Voriconazole (VFend) NDA 21-266. Center for Drug Evaluation and Research. Available at: http://www.fda.%20gov/cder/foi/nda/2002/21-266_21-267_Vfend.htm. Accessed November 8, 2004.
94.
Vfend (voriconazole) [package insert]. New York, NY: Pfizer; 2004.
95.
Luzzati R, Amalfitano G, Lazzarini L, el al. Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital. Eur J Clin Microbiol Infect Dis. 2000;19:602-607.
96.
Raad I, Hend H, BoktourM, et al. Management of central venous catheters in patients with cancer and candidemia. Clin Infect Dis. 2004;38:1119-1127.
97.
ColeGT, Halawa AA, Anaissie EJ. The role of the gastrointestinal tract in hematogenous candidiasis: from the laboratory to the bedside. Clin Infect Dis. 1996;22(suppl 2):S73-S88.
98.
Popp MB, Law EF, MacMillan BG. Parenteral nutrition in the burned child: a study of twenty-six patients. Ann Surg. 1974;179:219-225.
Warden GD, Wilmore DW, Pruitt BA. Central venous thrombosis: a hazard of medical progress. J Trauma. 1973;13:620-626.
101.
Henderson DK, Edwards JE, Montgomerie JZ. Hematogenous Candidaendophthalmitis in patients receiving parenteral hyperalimentation fluids. J Infect Dis. 1981;143:655-661.
102.
Strinden WD, Helgerson RB, Maki DG. Candida septic thrombosis of the great central veins associated with central catheters: clinical features and management. Ann Surg. 1985;202:653-658.
103.
Verghese A, Widrich WC, Arbeit RD. Central venous septic thrombophlebitis: the role of medical therapy. Medicine (Baltimore). 1985;64:394-400.
104.
Kaufman J, Demas C, Stark K, Flancbaum L.Catheter-related septic central venous thrombosis: current therapeutic options. West J Med. 1986;145:200-203.
105.
Baker CC, Peterson SR, SheldonGF. Septic phlebitis: a neglected disease. Am J Surg. 1979;138:97-103.
106.
Friedland G, von Reyn CF, Levy B, Arbeit R, Dasse P, Crumpacker C.Nosocomial endocarditis. Infect Control. 1984;5:284-288.
Pelletier LL Jr, Petersdorf RG. Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 1963-1972. Medicine (Baltimore). 1977;56:287-313.
109.
Calderwood SB, Swinski LA, Waternaux CM, et al. Risk factors for the development of prosthetic valve endocarditis. Circulation. 1985;72:31-37.
110.
Oelberg DG, Fisher DJ, GrossDM, et al. Endocarditis in high-risk neonates. Pediatrics. 1983;71:392-397.
111.
Rowley KM, Clubb KS, Smith GHW, et al. Right-sided infective endocarditis as a consequence of flow-directed pulmonary artery catherization. N Engl J Med. 1984;311:1152-1156.
112.
Raad II, Sabbagh MF. Optimal duration of therapy for catheterrelated Staphylococcus aureusbacteremia: a study of 55 cases and review. Clin Infect Dis. 1992;14:75-82.
113.
Cabell CH, Fowler VG. Importance of aggressive evaluation in patients with Staphylococcus aureusbacteremia. Am Heart J. 2004;147:379-380.
114.
Eykyn SJ. Staphylococcalsepsis: the changing pattern of disease and therapy. Lancet. 1988;1:100-104.
115.
Fowler VG, Sanders LL, Kong LK, et al. Infective endocarditis due to Staphylococcus aureus: 59 prospectively identified cases with follow-up. Clin Infect Dis. 1999;28:106-114.
116.
Hogevik H, Alestig K.Fungal endocarditis: a report on seven cases and a brief review. Infection. 1996;24:17-21.
117.
Wilson WR, Karchimer AW, Dajani AS, et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. JAMA. 1995;274:1706-1713.
118.
Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med. 1997;336:999-1007.
119.
Darling K, Singh J, Wilks D.Successful treatment of Candida glabrataendophthalmitis with amphotericin B lipid complex (ABLC). J Infect. 2000;40:92-94.
120.
Edwards JE Jr, Foos RY, Montgomerie JZ, Guze LB. Ocular manifestations of Candidasepticemia: review of seventy-six cases of hematogenousCandidaendophthalmitis. Medicine (Baltimore). 1974;53:47-75.
AklerME, Vellend H, McNeely DM, Walmsley SL, Gold WI. Use of fluconazole in the treatment of candidal endophthalmitis. Clin Infect Dis. 1995;20:657-664.
