Semin Respir Crit Care Med 2011; 32(2): 139-150
DOI: 10.1055/s-0031-1275526
© Thieme Medical Publishers

New Challenges in the Diagnosis, Management, and Prevention of Central Venous Catheter–Related Infections

Jean-François Timsit1 , 2 , Yohann Dubois1 , Clémence Minet1 , Agnès Bonadona1 , Maxime Lugosi1 , Claire Ara-Somohano1 , 2 , Rebecca Hamidfar-Roy1 , Carole Schwebel1
  • 1University Hospital Albert Michalon, Medical ICU, Grenoble, France
  • 2University Joseph Fourier, Albert Bonniot Institute, Grenoble, France
Further Information

Publication History

Publication Date:
19 April 2011 (online)

ABSTRACT

Catheters are the leading source of bloodstream infections in critically ill patients. Because the clinical signs of infection are nonspecific, such infections are overly suspected, which results in unnecessary removal of catheters. A conservative approach might be attempted in mild infections, whereas catheters should always be removed in cases of severe sepsis or septic shock. Nowadays, comprehensive unit-based improvement programs are effective to reduce catheter-related bloodstream infections (CR-BSIs). Rates of CR-BSI higher than 2 per 1000 catheter-days are no longer acceptable. A locally adapted checklist of preventive measures should include cutaneous antisepsis with alcoholic preparation, maximal barrier precaution, strict policy of catheter maintenance, and ablation of useless catheters. Antiseptic dressings and, to a lesser extent, antimicrobial-coated catheters, might be added to the prevention strategies if the level of infections remains high despite implementation of a prevention program. In the case of CR-BSI in intensive care units (ICUs), the catheter should be removed. In the case of persistence of fever or positive blood cultures after 3 days, inadequate antibiotic therapy, endocarditis, or thrombophlebitis should be ruled out.

REFERENCES

  • 1 Suetens C, Morales I, Savey A et al.. European surveillance of ICU-acquired infections (HELICS-ICU): methods and main results.  J Hosp Infect. 2007;  65 (Suppl 2) 171-173
  • 2 Mermel L A. Prevention of intravascular catheter-related infections.  Ann Intern Med. 2000;  132 (5) 391-402
  • 3 National Nosocomial Infections Surveillance System . National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004.  Am J Infect Control. 2004;  32 (8) 470-485
  • 4 Siempos I I, Kopterides P, Tsangaris I, Dimopoulou I, Armaganidis A E. Impact of catheter-related bloodstream infections on the mortality of critically ill patients: a meta-analysis.  Crit Care Med. 2009;  37 (7) 2283-2289
  • 5 Soufir L, Timsit J F, Mahe C, Carlet J, Regnier B, Chevret S. Attributable morbidity and mortality of catheter-related septicemia in critically ill patients: a matched, risk-adjusted, cohort study.  Infect Control Hosp Epidemiol. 1999;  20 (6) 396-401
  • 6 Warren D K, Quadir W W, Hollenbeak C S, Elward A M, Cox M J, Fraser V J. Attributable cost of catheter-associated bloodstream infections among intensive care patients in a nonteaching hospital.  Crit Care Med. 2006;  34 (8) 2084-2089
  • 7 Bouza E, Muñoz P, Burillo A Cardiovascular Infection Study Group et al. The challenge of anticipating catheter tip colonization in major heart surgery patients in the intensive care unit: are surface cultures useful?.  Crit Care Med. 2005;  33 (9) 1953-1960
  • 8 Liñares J, Sitges-Serra A, Garau J, Pérez J L, Martín R. Pathogenesis of catheter sepsis: a prospective study with quantitative and semiquantitative cultures of catheter hub and segments.  J Clin Microbiol. 1985;  21 (3) 357-360
  • 9 Lorente L, Jiménez A, Santana M et al.. Microorganisms responsible for intravascular catheter-related bloodstream infection according to the catheter site.  Crit Care Med. 2007;  35 (10) 2424-2427
  • 10 Sherertz R J, Raad I I, Belani A et al.. Three-year experience with sonicated vascular catheter cultures in a clinical microbiology laboratory.  J Clin Microbiol. 1990;  28 (1) 76-82
  • 11 Maki D G, Weise C E, Sarafin H W. A semiquantitative culture method for identifying intravenous-catheter-related infection.  N Engl J Med. 1977;  296 (23) 1305-1309
  • 12 Safdar N, Fine J P, Maki D G. Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection.  Ann Intern Med. 2005;  142 (6) 451-466
  • 13 Mermel L A, Allon M, Bouza E et al.. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America.  Clin Infect Dis. 2009;  49 (1) 1-45
  • 14 Souweine B, Heng A E, Aumeran C et al.. Do antibiotics administered at the time of central venous catheter removal interfere with the evaluation of colonization?.  Intensive Care Med. 2008;  34 (2) 286-291
  • 15 Vandecasteele S J, Van Eldere J, Merckx R, Peetermans W E. The effect of systemic antibiotics on the microbiological diagnosis of experimental foreign body infections caused by Staphylococcus epidermidis.  Diagn Microbiol Infect Dis. 2004;  48 (2) 89-95
  • 16 Armstrong C W, Mayhall C G, Miller K B et al.. Clinical predictors of infection of central venous catheters used for total parenteral nutrition.  Infect Control Hosp Epidemiol. 1990;  11 (2) 71-78
  • 17 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 (9184) 1071-1077
  • 18 Abdelkefi A, Achour W, Ben Othman T et al.. Difference in time to positivity is useful for the diagnosis of catheter-related bloodstream infection in hematopoietic stem cell transplant recipients.  Bone Marrow Transplant. 2005;  35 (4) 397-401
  • 19 Raad I, Hanna H A, Alakech B, Chatzinikolaou I, Johnson M M, Tarrand J. Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections.  Ann Intern Med. 2004;  140 (1) 18-25
  • 20 Bouza E, Alvarado N, Alcalá L, Pérez M J, Rincón C, Muñoz P. A randomized and prospective study of 3 procedures for the diagnosis of catheter-related bloodstream infection without catheter withdrawal.  Clin Infect Dis. 2007;  44 (6) 820-826
  • 21 Catton J A, Dobbins B M, Kite P et al.. In situ diagnosis of intravascular catheter-related bloodstream infection: a comparison of quantitative culture, differential time to positivity, and endoluminal brushing.  Crit Care Med. 2005;  33 (4) 787-791
  • 22 Guembe M, Rodríguez-Créixems M, Sánchez-Carrillo C, Pérez-Parra A, Martín-Rabadán P, Bouza E. How many lumens should be cultured in the conservative diagnosis of catheter-related bloodstream infections?.  Clin Infect Dis. 2010;  50 (12) 1575-1579
  • 23 Rijnders B J, Peetermans W E, Verwaest C, Wilmer A, Van Wijngaerden E. Watchful waiting versus immediate catheter removal in ICU patients with suspected catheter-related infection: a randomized trial.  Intensive Care Med. 2004;  30 (6) 1073-1080
  • 24 O'Grady N P, Alexander M, Dellinger E P Healthcare Infection Control Practices Advisory Committee et al. Guidelines for the prevention of intravascular catheter-related infections.  Infect Control Hosp Epidemiol. 2002;  23 (12) 759-769
  • 25 Ishikawa Y, Kiyama T, Haga Y et al.. Maximal sterile barrier precautions do not reduce catheter-related bloodstream infections in general surgery units: a multi-institutional randomized controlled trial.  Ann Surg. 2010;  251 (4) 620-623
  • 26 Raad I I, Hohn D C, Gilbreath B J et al.. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion.  Infect Control Hosp Epidemiol. 1994;  15 (4 Pt 1) 231-238
  • 27 Parienti J J, Thibon P, Heller R Antisepsie Chirurgicale des mains Study Group et al. Hand-rubbing with an aqueous alcoholic solution vs traditional surgical hand-scrubbing and 30-day surgical site infection rates: a randomized equivalence study.  JAMA. 2002;  288 (6) 722-727
  • 28 Chaiyakunapruk N, Veenstra D L, Lipsky B A, Saint S. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis.  Ann Intern Med. 2002;  136 (11) 792-801
  • 29 Vallés J, Fernández I, Alcaraz D et al.. Prospective randomized trial of 3 antiseptic solutions for prevention of catheter colonization in an intensive care unit for adult patients.  Infect Control Hosp Epidemiol. 2008;  29 (9) 847-853
  • 30 McDonnell G, Russell A D. Antiseptics and disinfectants: activity, action, and resistance.  Clin Microbiol Rev. 1999;  12 (1) 147-179
  • 31 Parienti J J, du Cheyron D, Ramakers M Members of the NACRE Study Group et al. Alcoholic povidone-iodine to prevent central venous catheter colonization: a randomized unit-crossover study.  Crit Care Med. 2004;  32 (3) 708-713
  • 32 Mimoz O, Villeminey S, Ragot S et al.. Chlorhexidine-based antiseptic solution vs alcohol-based povidone-iodine for central venous catheter care.  Arch Intern Med. 2007;  167 (19) 2066-2072
  • 33 Langgartner J, Linde H J, Lehn N, Reng M, Schölmerich J, Glück T. Combined skin disinfection with chlorhexidine/propanol and aqueous povidone-iodine reduces bacterial colonisation of central venous catheters.  Intensive Care Med. 2004;  30 (6) 1081-1088
  • 34 Merrer J, De Jonghe B, Golliot F French Catheter Study Group in Intensive Care et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial.  JAMA. 2001;  286 (6) 700-707
  • 35 Ruesch S, Walder B, Tramèr M R. Complications of central venous catheters: internal jugular versus subclavian access—a systematic review.  Crit Care Med. 2002;  30 (2) 454-460
  • 35a Timsit J F. Central venous access in intensive care unit patients: is the subclavian vein the royal route?.  Intensive Care Med. 2002;  28 (8) 1006-1008
  • 36 Parienti J J, Thirion M, Mégarbane B Members of the Cathedia Study Group et al. Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial.  JAMA. 2008;  299 (20) 2413-2422
  • 37 Timsit J F, Bruneel F, Cheval C et al.. Use of tunneled femoral catheters to prevent catheter-related infection: a randomized, controlled trial.  Ann Intern Med. 1999;  130 (9) 729-735
  • 38 Timsit J F, Sebille V, Farkas J C et al.. Effect of subcutaneous tunneling on internal jugular catheter-related sepsis in critically ill patients: a prospective randomized multicenter study.  JAMA. 1996;  276 (17) 1416-1420
  • 39 Hind D, Calvert N, McWilliams R et al.. Ultrasonic locating devices for central venous cannulation: meta-analysis.  BMJ. 2003;  327 (7411) 361
  • 40 Karakitsos D, Labropoulos N, De Groot E et al.. Real-time ultrasound-guided catheterisation of the internal jugular vein: a prospective comparison with the landmark technique in critical care patients.  Crit Care. 2006;  10 (6) R162
  • 41 Raad I I, Luna M, Khalil S A, Costerton J W, Lam C, Bodey G P. The relationship between the thrombotic and infectious complications of central venous catheters.  JAMA. 1994;  271 (13) 1014-1016
  • 42 Timsit J F, Farkas J C, Boyer J M et al.. Central vein catheter-related thrombosis in intensive care patients: incidence, risks factors, and relationship with catheter-related sepsis.  Chest. 1998;  114 (1) 207-213
  • 43 Mehall J R, Saltzman D A, Jackson R J, Smith S D. Fibrin sheath enhances central venous catheter infection.  Crit Care Med. 2002;  30 (4) 908-912
  • 44 Keller J E, Hindman J W, Mehall J R, Smith S D. Enoxaparin inhibits fibrin sheath formation and decreases central venous catheter colonization following bacteremic challenge.  Crit Care Med. 2006;  34 (5) 1450-1455
  • 45 Pierce C M, Wade A, Mok Q. Heparin-bonded central venous lines reduce thrombotic and infective complications in critically ill children.  Intensive Care Med. 2000;  26 (7) 967-972
  • 46 Abdelkefi A, Torjman L, Ladeb S et al.. Randomized trial of prevention of catheter-related bloodstream infection by continuous infusion of low-dose unfractionated heparin in patients with hematologic and oncologic disease.  J Clin Oncol. 2005;  23 (31) 7864-7870
  • 47 Timsit J F. Diagnosis and prevention of catheter-related infections.  Curr Opin Crit Care. 2007;  13 (5) 563-571
  • 48 Lucet J C, Bouadma L, Zahar J R et al.. Infectious risk associated with arterial catheters compared with central venous catheters.  Crit Care Med. 2010;  38 (4) 1030-1035
  • 49 Timsit J F, Schwebel C, Bouadma L Dressing Study Group et al. Chlorhexidine-impregnated sponges and less frequent dressing changes for prevention of catheter-related infections in critically ill adults: a randomized controlled trial.  JAMA. 2009;  301 (12) 1231-1241
  • 50 Ho K M. Comment on: use of chlorhexidine-impregnated dressing to prevent vascular and epidural catheter colonization and infection: a meta-analysis.  J Antimicrob Chemother. 2010;  65 (4) 811-814
  • 51 Garland J S, Alex C P, Mueller C D et al.. A randomized trial comparing povidone-iodine to a chlorhexidine gluconate-impregnated dressing for prevention of central venous catheter infections in neonates.  Pediatrics. 2001;  107 (6) 1431-1436
  • 52 Gillies D, O'Riordan L, Wallen M, Rankin K, Morrison A, Nagy S. Timing of intravenous administration set changes: a systematic review.  Infect Control Hosp Epidemiol. 2004;  25 (3) 240-250
  • 53 Bennett S N, McNeil M M, Bland L A et al.. Postoperative infections traced to contamination of an intravenous anesthetic, propofol.  N Engl J Med. 1995;  333 (3) 147-154
  • 54 Casey A L, Burnell S, Whinn H, Worthington T, Faroqui M H, Elliott T S. A prospective clinical trial to evaluate the microbial barrier of a needleless connector.  J Hosp Infect. 2007;  65 (3) 212-218
  • 55 Field K, McFarlane C, Cheng A C et al.. Incidence of catheter-related bloodstream infection among patients with a needleless, mechanical valve-based intravenous connector in an Australian hematology-oncology unit.  Infect Control Hosp Epidemiol. 2007;  28 (5) 610-613
  • 56 Maragakis L L, Bradley K L, Song X et al.. Increased catheter-related bloodstream infection rates after the introduction of a new mechanical valve intravenous access port.  Infect Control Hosp Epidemiol. 2006;  27 (1) 67-70
  • 57 Rupp M E, Sholtz L A, Jourdan D R et al.. Outbreak of bloodstream infection temporally associated with the use of an intravascular needleless valve.  Clin Infect Dis. 2007;  44 (11) 1408-1414
  • 58 Jarvis W R, Murphy C, Hall K K et al.. Health care-associated bloodstream infections associated with negative- or positive-pressure or displacement mechanical valve needleless connectors.  Clin Infect Dis. 2009;  49 (12) 1821-1827
  • 59 Veenstra D L, Saint S, Saha S, Lumley T, Sullivan S D. Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis.  JAMA. 1999;  281 (3) 261-267
  • 60 Walder B, Pittet D, Tramèr M R. 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 (12) 748-756
  • 61 Hockenhull J C, Dwan K M, Smith G W et al.. The clinical effectiveness of central venous catheters treated with anti-infective agents in preventing catheter-related bloodstream infections: a systematic review.  Crit Care Med. 2009;  37 (2) 702-712
  • 62 Tattawasart U, Maillard J Y, Furr J R, Russell A D. Development of resistance to chlorhexidine diacetate and cetylpyridinium chloride in Pseudomonas stutzeri and changes in antibiotic susceptibility.  J Hosp Infect. 1999;  42 (3) 219-229
  • 63 Falagas M E, Fragoulis K, Bliziotis I A, Chatzinikolaou I. Rifampicin-impregnated central venous catheters: a meta-analysis of randomized controlled trials.  J Antimicrob Chemother. 2007;  59 (3) 359-369
  • 64 Darouiche R O, Berger D H, Khardori N et al.. Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters: a randomized controlled trial.  Ann Surg. 2005;  242 (2) 193-200
  • 65 León C, Ruiz-Santana S, Rello J Cabaña Study Group et al. Benefits of minocycline and rifampin-impregnated central venous catheters: a prospective, randomized, double-blind, controlled, multicenter trial.  Intensive Care Med. 2004;  30 (10) 1891-1899
  • 66 Ramos E R, Reitzel R, Jiang Y et al.. Clinical effectiveness and risk of emerging resistance associated with prolonged use of antibiotic-impregnated catheters: more than 0.5 million catheter days and 7 years of clinical experience.  Crit Care Med. 2011;  39 (2) 245-251
  • 67 Noimark S, Dunnill C W, Wilson M, Parkin I P. The role of surfaces in catheter-associated infections.  Chem Soc Rev. 2009;  38 (12) 3435-3448
  • 68 Garland J S, Alex C P, Henrickson K J, McAuliffe T L, Maki D G. A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial.  Pediatrics. 2005;  116 (2) e198-e205
  • 69 Yahav D, Rozen-Zvi B, Gafter-Gvili A, Leibovici L, Gafter U, Paul M. Antimicrobial lock solutions for the prevention of infections associated with intravascular catheters in patients undergoing hemodialysis: systematic review and meta-analysis of randomized, controlled trials.  Clin Infect Dis. 2008;  47 (1) 83-93
  • 70 Raad I I, Fang X, Keutgen X M, Jiang Y, Sherertz R, Hachem R. The role of chelators in preventing biofilm formation and catheter-related bloodstream infections.  Curr Opin Infect Dis. 2008;  21 (4) 385-392
  • 71 Jurewitsch B, Jeejeebhoy K N. Taurolidine lock: the key to prevention of recurrent catheter-related bloodstream infections.  Clin Nutr. 2005;  24 (3) 462-465
  • 72 Sherertz R J, Boger M S, Collins C A, Mason L, Raad I I. Comparative in vitro efficacies of various catheter lock solutions.  Antimicrob Agents Chemother. 2006;  50 (5) 1865-1868
  • 73 Solomon L R, Cheesbrough J S, Ebah L et al.. A randomized double-blind controlled trial of taurolidine-citrate catheter locks for the prevention of bacteremia in patients treated with hemodialysis.  Am J Kidney Dis. 2010;  55 (6) 1060-1068
  • 74 Raad I, Hanna H, Dvorak T, Chaiban G, Hachem R. Optimal antimicrobial catheter lock solution, using different combinations of minocycline, EDTA, and 25-percent ethanol, rapidly eradicates organisms embedded in biofilm.  Antimicrob Agents Chemother. 2007;  51 (1) 78-83
  • 75 Onland W, Shin C E, Fustar S, Rushing T, Wong W Y. Ethanol-lock technique for persistent bacteremia of long-term intravascular devices in pediatric patients.  Arch Pediatr Adolesc Med. 2006;  160 (10) 1049-1053
  • 76 Balestrino D, Souweine B, Charbonnel N et al.. Eradication of microorganisms embedded in biofilm by an ethanol-based catheter lock solution.  Nephrol Dial Transplant. 2009;  24 (10) 3204-3209
  • 77 Sanders J, Pithie A, Ganly P et al.. A prospective double-blind randomized trial comparing intraluminal ethanol with heparinized saline for the prevention of catheter-associated bloodstream infection in immunosuppressed haematology patients.  J Antimicrob Chemother. 2008;  62 (4) 809-815
  • 78 Slobbe L, Doorduijn J K, Lugtenburg P J et al.. Prevention of catheter-related bacteremia with a daily ethanol lock in patients with tunnelled catheters: a randomized, placebo-controlled trial.  PLoS ONE. 2010;  5 (5) e10840
  • 79 Gastmeier P, Geffers C, Brandt C et al.. Effectiveness of a nationwide nosocomial infection surveillance system for reducing nosocomial infections.  J Hosp Infect. 2006;  64 (1) 16-22
  • 80 Shapey I M, Foster M A, Whitehouse T, Jumaa P, Bion J F. Central venous catheter-related bloodstream infections: improving post-insertion catheter care.  J Hosp Infect. 2009;  71 (2) 117-122
  • 81 Trick W E, Vernon M O, Welbel S F, Wisniewski M F, Jernigan J A, Weinstein R A. Unnecessary use of central venous catheters: the need to look outside the intensive care unit.  Infect Control Hosp Epidemiol. 2004;  25 (3) 266-268
  • 82 Eggimann P, Hugonnet S, Sax H, Harbarth S, Chevrolet J C, Pittet D. Long-term reduction of vascular access-associated bloodstream infection.  Ann Intern Med. 2005;  142 (10) 875-876
  • 83 Khouli H, Jahnes K, Shapiro J et al.. Performance of medical residents in sterile techniques during central vein catheterization: randomized trial of efficacy of simulation-based training.  Chest. 2011;  139 (1) 80-87
  • 84 Barsuk J H, Cohen E R, Feinglass J, McGaghie W C, Wayne D B. Use of simulation-based education to reduce catheter-related bloodstream infections.  Arch Intern Med. 2009;  169 (15) 1420-1423
  • 85 Gastmeier P, Geffers C. Prevention of catheter-related bloodstream infections: analysis of studies published between 2002 and 2005.  J Hosp Infect. 2006;  64 (4) 326-335
  • 86 Pronovost P, Needham D, Berenholtz S et al.. An intervention to decrease catheter-related bloodstream infections in the ICU.  N Engl J Med. 2006;  355 (26) 2725-2732
  • 87 Pérez Parra A, Cruz Menárguez M, Pérez Granda M J, Tomey M J, Padilla B, Bouza E. A simple educational intervention to decrease incidence of central line-associated bloodstream infection (CLABSI) in intensive care units with low baseline incidence of CLABSI.  Infect Control Hosp Epidemiol. 2010;  31 (9) 964-967
  • 88 Sawyer M, Weeks K, Goeschel C A et al.. Using evidence, rigorous measurement, and collaboration to eliminate central catheter-associated bloodstream infections.  Crit Care Med. 2010;  38 (8, Suppl) S292-S298
  • 89 Shuman E K, Washer L L, Arndt J L et al.. Analysis of central line-associated bloodstream infections in the intensive care unit after implementation of central line bundles.  Infect Control Hosp Epidemiol. 2010;  31 (5) 551-553
  • 90 Pronovost P J, Goeschel C A, Colantuoni E et al.. Sustaining reductions in catheter related bloodstream infections in Michigan intensive care units: observational study.  BMJ. 2010;  340 c309
  • 91 Lin M Y, Hota B, Khan Y M CDC Prevention Epicenter Program et al. Quality of traditional surveillance for public reporting of nosocomial bloodstream infection rates.  JAMA. 2010;  304 (18) 2035-2041
  • 92 Niedner M F. 2008 National Association of Children's Hospitals and Related Institutions Pediatric Intensive Care Unit Patient Care FOCUS Group . The harder you look, the more you find: catheter-associated bloodstream infection surveillance variability.  Am J Infect Control. 2010;  38 (8) 585-595
  • 93 Carlet J, Fabry J, Amalberti R, Degos L. The “zero risk” concept for hospital-acquired infections: a risky business!.  Clin Infect Dis. 2009;  49 (5) 747-749
  • 94 Raad I, Hanna H, Maki D. Intravascular catheter-related infections: advances in diagnosis, prevention, and management.  Lancet Infect Dis. 2007;  7 (10) 645-657
  • 95 Nucci M, Anaissie E, Betts R F et al.. Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials.  Clin Infect Dis. 2010;  51 (3) 295-303
  • 96 Ekkelenkamp M B, van der Bruggen T, van de Vijver D A, Wolfs T F, Bonten M J. Bacteremic complications of intravascular catheters colonized with Staphylococcus aureus.  Clin Infect Dis. 2008;  46 (1) 114-118
  • 97 Pérez-Parra A, Muñoz P, Guinea J, Martín-Rabadán P, Guembe M, Bouza E. Is Candida colonization of central vascular catheters in non-candidemic, non-neutropenic patients an indication for antifungals?.  Intensive Care Med. 2009;  35 (4) 707-712
  • 98 Roberts J A, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient.  Crit Care Med. 2009;  37 (3) 840-851 quiz 859
  • 99 Frank D A, Meuse J, Hirsch D, Ibrahim J G, van den Abbeele A D. The treatment and outcome of cancer patients with thromboses on central venous catheters.  J Thromb Thrombolysis. 2000;  10 (3) 271-275
  • 100 Rehm S J, Boucher H, Levine D et al.. Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates.  J Antimicrob Chemother. 2008;  62 (6) 1413-1421
  • 101 Lodise T P, Miller C D, Graves J et al.. Predictors of high vancomycin MIC values among patients with methicillin-resistant Staphylococcus aureus bacteraemia.  J Antimicrob Chemother. 2008;  62 (5) 1138-1141
  • 102 Falagas M E, Vardakas K Z, Athanasiou S. Intravenous heparin in combination with antibiotics for the treatment of deep vein septic thrombophlebitis: a systematic review.  Eur J Pharmacol. 2007;  557 (2-3) 93-98

Jean-François TimsitM.D. Ph.D. 

University Hospital Albert Michalon, BP 217

38043 Grenoble CEDEX 9, France

Email: jftimsit@chu-grenoble.fr