Antibiotic Stewardship in the Intensive Care Unit

ABSTRACT

Antimicrobial stewardship encompasses the optimization of agent selection, dose, and duration leading to the best clinical outcome in the treatment or prevention of infection. Ideally, these goals are met while producing the fewest side effects and lowest risk for subsequent resistance. The concept of antimicrobial stewardship can be directly applied to the prescription of empirical antibiotic therapy in the intensive care unit (ICU) because it is well described that inappropriate initial regimens lead to increased mortality. As such, care should be taken to identify factors that place patients at risk for infection with pathogens demonstrating reduced susceptibility or multidrug resistance. Research efforts have concentrated on molecular diagnostic techniques to aid in more rapid organism detection and thus potential for earlier therapy appropriateness and deescalation, although limitations prohibiting widespread implementation of this technology exist. Also of great importance with regard to stewardship efforts is infection prevention. Effective prophylactic strategies reduce the occurrence of nosocomial infections and may therefore improve patient outcomes while obviating the need for otherwise necessary antimicrobial exposure.

Antibiotic stewardship - infection - intensive care unit

REFERENCES

• 1 Spellberg B, Guidos R, Gilbert D Infectious Diseases Society of America et al. The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America.  Clin Infect Dis. 2008;  46 (2) 155-164
• 2 Kollef M H, Sherman G, Ward S, Fraser V J. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients.  Chest. 1999;  115 (2) 462-474
• 3 Micek S, Welch E, Khan J et al.. Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to gram-negative bacteria: a retrospective analysis.  Antimicrob Agents Chemother. 2010;  54 (5) 1742-1748
• 4 Arnold H M, Micek S T, Shorr A F et al.. Hospital resource utilization and costs of inappropriate treatment of candidemia.  Pharmacotherapy. 2010;  30 (4) 361-368
• 5 Zilberberg M D, Shorr A F, Micek S T et al.. Epidemiology and outcomes of hospitalizations with complicated skin and skin-structure infections: implications of healthcare-associated infection risk factors.  Infect Control Hosp Epidemiol. 2009;  30 (12) 1203-1210
• 6 Micek S T, Kollef K E, Reichley R M, Roubinian N, Kollef M H. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience.  Antimicrob Agents Chemother. 2007;  51 (10) 3568-3573
• 7 Kollef K E, Schramm G E, Wills A R, Reichley R M, Micek S T, Kollef M H. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria.  Chest. 2008;  134 (2) 281-287
• 8 Arias C A, Murray B E. Antibiotic-resistant bugs in the 21st century—a clinical super-challenge.  N Engl J Med. 2009;  360 (5) 439-443
• 9 Pakyz A L, MacDougall C, Oinonen M, Polk R E. Trends in antibacterial use in US academic health centers: 2002 to 2006.  Arch Intern Med. 2008;  168 (20) 2254-2260
• 10 Kollef M H, Napolitano L M, Solomkin J S et al.. Health care-associated infection (HAI): a critical appraisal of the emerging threat-proceedings of the HAI Summit.  Clin Infect Dis. 2008;  47 (Suppl 2) S55-S99, quiz S100–S101
• 11 Bhat S V, Peleg A Y, Lodise Jr T P et al.. Failure of current cefepime breakpoints to predict clinical outcomes of bacteremia caused by gram-negative organisms.  Antimicrob Agents Chemother. 2007;  51 (12) 4390-4395
• 12 Tam V H, Gamez E A, Weston J S et al.. Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin-tazobactam: implications on the appropriateness of the resistance breakpoint.  Clin Infect Dis. 2008;  46 (6) 862-867
• 13 Soriano A, Marco F, Martínez J A et al.. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia.  Clin Infect Dis. 2008;  46 (2) 193-200
• 14 Bhat S, Fujitani S, Potoski B A et al.. Pseudomonas aeruginosa infections in the Intensive Care Unit: can the adequacy of empirical beta-lactam antibiotic therapy be improved?.  Int J Antimicrob Agents. 2007;  30 (5) 458-462
• 15 El Amari E B, Chamot E, Auckenthaler R, Pechère J C, Van Delden C. Influence of previous exposure to antibiotic therapy on the susceptibility pattern of Pseudomonas aeruginosa bacteremic isolates.  Clin Infect Dis. 2001;  33 (11) 1859-1864
• 16 Beardsley J R, Williamson J C, Johnson J W, Ohl C A, Karchmer T B, Bowton D L. Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia.  Chest. 2006;  130 (3) 787-793
• 17 Lancaster J W, Lawrence K R, Fong J J et al.. Impact of an institution-specific hospital-acquired pneumonia protocol on the appropriateness of antibiotic therapy and patient outcomes.  Pharmacotherapy. 2008;  28 (7) 852-862
• 18 Aarts M A, Hancock J N, Heyland D, McLeod R S, Marshall J C. Empiric antibiotic therapy for suspected ventilator-associated pneumonia: a systematic review and meta-analysis of randomized trials.  Crit Care Med. 2008;  36 (1) 108-117
• 19 Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials.  BMJ. 2004;  328 (7441) 668
• 20 Heyland D K, Dodek P, Muscedere J, Day A, Cook D. Group CCCT . Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia.  Crit Care Med. 2008;  36 (3) 737-744
• 21 Kumar A, Zarychanski R, Light B Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group et al. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.  Crit Care Med. 2010;  38 (9) 1773-1785
• 22 Schentag J J, Strenkoski-Nix L C, Nix D E, Forrest A. Pharmacodynamic interactions of antibiotics alone and in combination.  Clin Infect Dis. 1998;  27 (1) 40-46
• 23 Nicasio A M, Ariano R E, Zelenitsky S A et al.. Population pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill patients with ventilator-associated pneumonia.  Antimicrob Agents Chemother. 2009;  53 (4) 1476-1481
• 24 Van Wart S A, Andes D R, Ambrose P G, Bhavnani S M. Pharmacokinetic-pharmacodynamic modeling to support doripenem dose regimen optimization for critically ill patients.  Diagn Microbiol Infect Dis. 2009;  63 (4) 409-414
• 25 Roberts J A, Kirkpatrick C M, Roberts M S, Dalley A J, Lipman J. First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis.  Int J Antimicrob Agents. 2010;  35 (2) 156-163
• 26 Chastre J, Wunderink R, Prokocimer P, Lee M, Kaniga K, Friedland I. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study.  Crit Care Med. 2008;  36 (4) 1089-1096
• 27 Patel GWPN, Patel N, Lat A et al.. Outcomes of extended infusion piperacillin/tazobactam for documented gram-negative infections.  Diagn Microbiol Infect Dis. 2009;  64 (2) 236-240
• 28 Shafazand S, Weinacker A B. Blood cultures in the critical care unit: improving utilization and yield.  Chest. 2002;  122 (5) 1727-1736
• 29 Bates D W, Goldman L, Lee T H. Contaminant blood cultures and resource utilization: the true consequences of false-positive results.  JAMA. 1991;  265 (3) 365-369
• 30 Ince J, McNally A. Development of rapid, automated diagnostics for infectious disease: advances and challenges.  Expert Rev Med Devices. 2009;  6 (6) 641-651
• 31 Biedenbach D J, Moet G J, Jones R N. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002).  Diagn Microbiol Infect Dis. 2004;  50 (1) 59-69
• 32 Forrest G N, Roghmann M C, Toombs L S et al.. Peptide nucleic acid fluorescent in situ hybridization for hospital-acquired enterococcal bacteremia: delivering earlier effective antimicrobial therapy.  Antimicrob Agents Chemother. 2008;  52 (10) 3558-3563
• 33 Forrest G N, Mehta S, Weekes E, Lincalis D P, Johnson J K, Venezia R A. Impact of rapid in situ hybridization testing on coagulase-negative staphylococci positive blood cultures.  J Antimicrob Chemother. 2006;  58 (1) 154-158
• 34 Søgaard M, Hansen D S, Fiandaca M J, Stender H, Schønheyder H C. Peptide nucleic acid fluorescence in situ hybridization for rapid detection of Klebsiella pneumoniae from positive blood cultures.  J Med Microbiol. 2007;  56 (Pt 7) 914-917
• 35 Søgaard M, Stender H, Schønheyder H C. Direct identification of major blood culture pathogens, including Pseudomonas aeruginosa and Escherichia coli, by a panel of fluorescence in situ hybridization assays using peptide nucleic acid probes.  J Clin Microbiol. 2005;  43 (4) 1947-1949
• 36 Peleg A Y, Tilahun Y, Fiandaca M J et al.. Utility of peptide nucleic acid fluorescence in situ hybridization for rapid detection of Acinetobacter spp. and Pseudomonas aeruginosa.  J Clin Microbiol. 2009;  47 (3) 830-832
• 37 Pfaller M A, Diekema D J. Epidemiology of invasive candidiasis: a persistent public health problem.  Clin Microbiol Rev. 2007;  20 (1) 133-163
• 38 Trick W E, Fridkin S K, Edwards J R, Hajjeh R A, Gaynes R P. Hospitals TNNISS . Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999.  Clin Infect Dis. 2002;  35 (5) 627-630
• 39 Pfaller M A, Diekema D J, Gibbs D L Global Antifungal Surveillance Study et al. Results from the ARTEMIS DISK Global Antifungal Surveillance study, 1997 to 2005: an 8.5-year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing.  J Clin Microbiol. 2007;  45 (6) 1735-1745
• 40 Shepard J R, Addison R M, Alexander B D et al.. Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles.  J Clin Microbiol. 2008;  46 (1) 50-55
• 41 Gherna M, Merz W G. Identification of Candida albicans and Candida glabrata within 1.5 hours directly from positive blood culture bottles with a shortened peptide nucleic acid fluorescence in situ hybridization protocol.  J Clin Microbiol. 2009;  47 (1) 247-248
• 42 Alexander B D, Ashley E D, Reller L B, Reed S D. Cost savings with implementation of PNA FISH testing for identification of Candida albicans in blood cultures.  Diagn Microbiol Infect Dis. 2006;  54 (4) 277-282
• 43 Forrest G N, Mankes K, Jabra-Rizk M A et al.. Peptide nucleic acid fluorescence in situ hybridization-based identification of Candida albicans and its impact on mortality and antifungal therapy costs.  J Clin Microbiol. 2006;  44 (9) 3381-3383
• 44 Lehmann L E, Alvarez J, Hunfeld K P et al.. Potential clinical utility of polymerase chain reaction in microbiological testing for sepsis.  Crit Care Med. 2009;  37 (12) 3085-3090
• 45 Bloos F, Hinder F, Becker K et al.. A multicenter trial to compare blood culture with polymerase chain reaction in severe human sepsis.  Intensive Care Med. 2010;  36 (2) 241-247
• 46 Kilic A, Muldrew K L, Tang Y W, Basustaoglu A C. Triplex real-time polymerase chain reaction assay for simultaneous detection of Staphylococcus aureus and coagulase-negative staphylococci and determination of methicillin resistance directly from positive blood culture bottles.  Diagn Microbiol Infect Dis. 2010;  66 (4) 349-355
• 47 Stamper P D, Babiker W, Alcabasa R et al.. Evaluation of a new commercial TaqMan PCR assay for direct detection of the Clostridium difficile toxin B gene in clinical stool specimens.  J Clin Microbiol. 2009;  47 (12) 3846-3850
• 48 Kvach E J, Ferguson D, Riska P F, Landry M L. Comparison of BD GeneOhm Cdiff real-time PCR assay with a two-step algorithm and a toxin A/B enzyme-linked immunosorbent assay for diagnosis of toxigenic Clostridium difficile infection.  J Clin Microbiol. 2010;  48 (1) 109-114
• 49 Micek S T, Heuring T J, Hollands J M, Shah R A, Kollef M H. Optimizing antibiotic treatment for ventilator-associated pneumonia.  Pharmacotherapy. 2006;  26 (2) 204-213
• 50 Eachempati S R, Hydo L J, Shou J, Barie P S. Does de-escalation of antibiotic therapy for ventilator-associated pneumonia affect the likelihood of recurrent pneumonia or mortality in critically ill surgical patients?.  J Trauma. 2009;  66 (5) 1343-1348
• 51 American Thoracic Society . Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.  Am J Respir Crit Care Med. 2005;  171 (4) 388-416
• 52 Labelle A J, Arnold H, Reichley R M, Micek S T, Kollef M H. A comparison of culture-positive and culture-negative health-care-associated pneumonia.  Chest. 2010;  137 (5) 1130-1137
• 53 Schlueter M, James C, Dominguez A, Tsu L, Seymann G. Practice patterns for antibiotic de-escalation in culture-negative healthcare-associated pneumonia.  Infection. 2010;  38 (5) 357-362
• 54 Stoutenbeek C P, van Saene H K, Miranda D R, Zandstra D F. The effect of selective decontamination of the digestive tract on colonisation and infection rate in multiple trauma patients.  Intensive Care Med. 1984;  10 (4) 185-192
• 55 van Nieuwenhoven C A, Buskens E, van Tiel F H, Bonten M J. Relationship between methodological trial quality and the effects of selective digestive decontamination on pneumonia and mortality in critically ill patients.  JAMA. 2001;  286 (3) 335-340
• 56 de Jonge E, Schultz M J, Spanjaard L et al.. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.  Lancet. 2003;  362 (9389) 1011-1016
• 57 Krueger W A, Lenhart F P, Neeser G et al.. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial.  Am J Respir Crit Care Med. 2002;  166 (8) 1029-1037
• 58 de La Cal M A, Cerdá E, García-Hierro P et al.. Survival benefit in critically ill burned patients receiving selective decontamination of the digestive tract: a randomized, placebo-controlled, double-blind trial.  Ann Surg. 2005;  241 (3) 424-430
• 59 Chan E Y, Ruest A, Meade M O, Cook D J. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis.  BMJ. 2007;  334 (7599) 889-900
• 60 de Smet A M, Kluytmans J A, Cooper B S et al.. Decontamination of the digestive tract and oropharynx in ICU patients.  N Engl J Med. 2009;  360 (1) 20-31
• 61 Lingnau W, Berger J, Javorsky F, Fille M, Allerberger F, Benzer H. Changing bacterial ecology during a five-year period of selective intestinal decontamination.  J Hosp Infect. 1998;  39 (3) 195-206
• 62 Oostdijk E A, de Smet A M, Blok H E et al.. Ecological effects of selective decontamination on resistant gram-negative bacterial colonization.  Am J Respir Crit Care Med. 2010;  181 (5) 452-457
• 63 Verwaest C, Verhaegen J, Ferdinande P et al.. Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit.  Crit Care Med. 1997;  25 (1) 63-71
• 64 Hammond J M, Potgieter P D, Saunders G L, Forder A A. Double-blind study of selective decontamination of the digestive tract in intensive care.  Lancet. 1992;  340 (8810) 5-9
• 65 DeRiso II A J, Ladowski J S, Dillon T A, Justice J W, Peterson A C. Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery.  Chest. 1996;  109 (6) 1556-1561
• 66 Segers P, Speekenbrink R G, Ubbink D T, van Ogtrop M L, de Mol B A. Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: a randomized controlled trial.  JAMA. 2006;  296 (20) 2460-2466
• 67 Fourrier F, Cau-Pottier E, Boutigny H, Roussel-Delvallez M, Jourdain M, Chopin C. Effects of dental plaque antiseptic decontamination on bacterial colonization and nosocomial infections in critically ill patients.  Intensive Care Med. 2000;  26 (9) 1239-1247
• 68 Fourrier F, Dubois D, Pronnier P PIRAD Study Group et al. Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study.  Crit Care Med. 2005;  33 (8) 1728-1735
• 69 Panchabhai T S, Dangayach N S, Krishnan A, Kothari V M, Karnad D R. Oropharyngeal cleansing with 0.2% chlorhexidine for prevention of nosocomial pneumonia in critically ill patients: an open-label randomized trial with 0.01% potassium permanganate as control.  Chest. 2009;  135 (5) 1150-1156
• 70 Koeman M, van der Ven A J, Hak E et al.. Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia.  Am J Respir Crit Care Med. 2006;  173 (12) 1348-1355
• 71 Tantipong H, Morkchareonpong C, Jaiyindee S, Thamlikitkul V. Randomized controlled trial and meta-analysis of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia.  Infect Control Hosp Epidemiol. 2008;  29 (2) 131-136
• 72 Kola A, Gastmeier P. Efficacy of oral chlorhexidine in preventing lower respiratory tract infections: meta-analysis of randomized controlled trials.  J Hosp Infect. 2007;  66 (3) 207-216
• 73 Chlebicki M P, Safdar N. Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis.  Crit Care Med. 2007;  35 (2) 595-602
• 74 Bratzler D W, Houck P M. Workgroup SIPGW . Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project.  Clin Infect Dis. 2004;  38 (12) 1706-1715
• 75 The Joint Commission .Available at: http://www.outcome.com/provider-joint-commission.htm Accessed September 9, 2010
• 76 Bratzler D W, Houck P M, Richards C et al.. Use of antimicrobial prophylaxis for major surgery: baseline results from the National Surgical Infection Prevention Project.  Arch Surg. 2005;  140 (2) 174-182
• 77 Burke J F. The effective period of preventive antibiotic action in experimental incisions and dermal lesions.  Surgery. 1961;  50 161-168
• 78 Stone H H, Hooper C A, Kolb L D, Geheber C E, Dawkins E J. Antibiotic prophylaxis in gastric, biliary and colonic surgery.  Ann Surg. 1976;  184 (4) 443-452
• 79 Classen D C, Evans R S, Pestotnik S L, Horn S D, Menlove R L, Burke J P. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection.  N Engl J Med. 1992;  326 (5) 281-286
• 80 Terpstra S, Noordhoek G T, Voesten H G, Hendriks B, Degener J E. Rapid emergence of resistant coagulase-negative staphylococci on the skin after antibiotic prophylaxis.  J Hosp Infect. 1999;  43 (3) 195-202
• 81 Harbarth S, Samore M H, Lichtenberg D, Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infections and antimicrobial resistance.  Circulation. 2000;  101 (25) 2916-2921
• 82 Hoth J J, Franklin G A, Stassen N A, Girard S M, Rodriguez R J, Rodriguez J L. Prophylactic antibiotics adversely affect nosocomial pneumonia in trauma patients.  J Trauma. 2003;  55 (2) 249-254
• 83 Smith D W. Decreased antimicrobial resistance following changes in antibiotic use.  Surg Infect (Larchmt). 2000;  1 (1) 73-78
• 84 Nicastri E, Leone S, Petrosillo N et al.. Decrease of methicillin resistant Staphylococcus aureus prevalence after introduction of a surgical antibiotic prophylaxis protocol in an Italian hospital.  New Microbiol. 2008;  31 (4) 519-525
• 85 Meyer E, Schwab F, Pollitt A, Bettolo W, Schroeren-Boersch B, Trautmann M. Impact of a change in antibiotic prophylaxis on total antibiotic use in a surgical intensive care unit.  Infection. 2010;  38 (1) 19-24