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2008 30% 2008 2008 2004 813 386 07-346-8339 E-mail srwann@vghks.gov.tw 66

30% 2008 1 2008 2008 Intensive Care Med (2008)34:17-60 67

2 3 C activated protein C 4 5,6 65% JAMA 1995;273(2):117-23 Circulation, 1970;41:989-1001 30% 3% 1C 68

70% 90-95% 7 10 8 9 2004 14.6% 11.7% 70.3% 29.7% 3.7% 15.8% Escherichia coli 30.8% Klebsiella pneumoniae 16.6% Staphylococcus aureus 15.4% Streptococcus spp. 8.6% 80% gentamicin cefazolin gentamicin 90% 28 extended spectrum lactamase, ESBL 17 9 89% 11% carbapenem amikacin 71% 1C 7.6% 10 1D 1B 1D Crit Care Med 2006;34:1589-1596 69

communityacquired infection hospital-acquired infection health-care associated infection 1B 11 12 vancomycin amikacin superinfection Candida spp.clostridium difficile vancomycin-resistant enterococcus, VRE 1C combination therapy Pseudomonas aeruginosa 13 2D 14 2D 3 5 2D de-escalation therapy 7 10 1D 1D 15 70

1C 6 1D 1C 16 2B 17 1D 18 bacteria translocation 19 Acinetobacter baumannii ciprofloxacin 20 outbreak surveillance cohort isolation 21 cefazolin gentamicin 95% piperacillin amikacin 84% ORSA vancomycin teicoplanin cohort isolation 01. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008, Intensive Care Med. 2008;34:17-60. 02. Rangel-Frausto MS, Pittet D, Costigan M, et al. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA. 1995; 273:117-123. 03. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999;341:586-592. 04. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. N Engl J Med. 2001;344: 699-709. 05. Weil MH, Afifi AA. Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation. 1970; 41:989-1001. 06. Trzeciak S, Dellinger RP, Chansky ME, et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med. 2007;33:970-977. 07. Weinstein MP, Reller LP, Murphy JR, et al. The clinical significance of positive blood cultures: A comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis 1983;5:35-53. 08. Mermel LA, Maki DG. Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood. Ann Intern Med 1993;119:270-272. 09. American Thoracic Society, Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit 71

Care Med 2005;171:388-416. 10. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-1596. 11. Ali MZ, Goetz MB A meta-analysis of the relative efficacy and toxicity of single daily dosing versus multiple daily dosing of aminoglycosides. Clin Infec Dis 1997;24:796-809. 12. Pea F, Viale P, Furlanut M. Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability. Clin Pharmacokinet. 2005; 44:1009-1934. 13. Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis. 2004;4:519-527. 14. Klastersky J. Management of fever in neutropenic patients with different risks of complications. Clin Infect Dis 2004;39:S32-37. 15. Jimenez MF, Marshall JC. Source control in the management of sepsis. Intensive Care Med 2001;27: S49-S62. 16. Moss RL, Musemeche CA, Kosloske AM. Necrotizing fascitis in children: prompt recognition and aggressive therapy improve survival. J Pediatr Surg 1996;31:1142-1146. 17. Bufalari A, Giustozzi G, Moggi L. Postoperative intraabdominal abscesses: Percutaneous versus surgical treatment. Acta Chir Belg 1996;96:197-200. 18. O'Grady NP, Alexander M, Dellinger EP, ET AL. Healthcare Infection Control Practices Advisory Committee Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis 2002;35: 1281-1307. 19. Marshall JC, Christou NV, Meakins JL. The gastrointestinal tract. The "undrained abscess" of multiple organ failure. Ann Surg. 1993;218:111-119. 20. Hsueh PR, Teng LJ, Chen CY, ET AL. Pandrugresistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan. Infect Dis. 2002;8:827-832. 21. Corbella X, Montero A, Pujol M, ET AL. Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii. J Clin Microbiol. 2000;38: 4086-4095. 72

SURVIVING SEPSIS CAMPAIGN 2008: INFECTION ISSUE Shue-Ren Wann Abstract There is a continuum of clinical events from infection to systemic inflammatory response syndrome (SIRS) to severe sepsis to septic shock. The rates of morbidity, bacteremia and mortality increase over time. In this era of modern critical care, the mortality rate of septic shock remains relatively high. Approximately 30% of patients with septic shock die, and sepsis remains to be the main cause of death in critically ill patients. To effectively manage septicemia and thus lower the mortality rate of patients with sepsis, the issues of infectious diseases should be tackled seriously. The 2008 Surviving Sepsis Campaign Guideline for the "infection issues" were divided into 3 categories - the infection diagnosis, antibiotic therapy and source control. The diagnosis of infection (sepsis) is influenced mainly by 2 important factors - the determination of the pathogen causing the disease and the evaluation of the severity of the patient. The former provides the basis of the selection of antibiotic agents while the latter confers an assessment of the hemodynamic status of the patient. The measurement of serum lactate levels, coagulation profiles and mixed venous oxygen saturation could provide quantitation of the severity of the sepsis. Appropriate and timely administration of antibiotic agents is one of the most crucial factors in the management of the patient. Antibiotic agents should be given within one hour after a patient presents with severe sepsis or septic shock. Microbiologic cultures should be done prior to the administration of the antibiotic agents. The selection of empiric antibiotic agent is done after obtaining a detailed clinical history and meticulous physical examination along with laboratory, radiologic and invasive diagnostic procedures. Administration of a broad-spectrum antibiotic agent in the absence of adequate drainage and debridement may lead to prolongation of antibiotic treatment and the inevitable emergence of bacterial resistance. In this article, we concisely introduce infection and sepsis, the evaluation of an infected patient, the analysis of bacteremia of adult patients in the emergency department of Kaohsiung Veterans General Hospital in 2004, the principles of antibiotic usage, aggressive eradication of the source of infection and the control of emerging resistant pathogens. Key words: Sepsis, Septic shock, Antibiotic therapy, Source control Correspondence: Dr. Shue-Ren Wann Emergency Medicine Division, Kaohsiung Veterans General Hospital, No.386, Ta-Chung 1st Rd., Kaohsiung City 813, Taiwan Phone: 886-7-346-8339; E-mail: srwann@vghks.gov.tw 73