The document discusses principles for antibiotic use in critically ill patients, including: 1) Starting with broad-spectrum empiric therapy based on local microbiological data and guidelines. 2) Reassessing and de-escalating treatment based on culture results and the patient's clinical response. 3) Factors that increase the risk of resistant pathogens like hospital-acquired infections require broader initial coverage.

1. 重症病患之抗生素使用原則 財團法人為恭紀念醫院 感染科 曾政尹 醫師 C.Y.T.

5. Golden Triangle Antimicrobial agent Microorganism Host Immune system Microbiological profile Pharmacokinetics C.Y.T.

7. Initial Selection of Antibiotics SUSPECTED DIAGNOSIS CLINICAL EVALUATION (site of infection, host, lab. data) C.Y.T.

13. Getting It Right From Start To Finish The Role of De-escalation Therapy C.Y.T.

17. Local microbiological data

19. Choose broad-spectrum, empiric treatment regimen based on clinical symptoms and unit-specific antibiogram data and guidelines . Obtain culture prior to antibiotic administration. Obtain and analyze microbiological data Modify regimen accordingly Reassess patient Process for Initial Appropriate Therapy C.Y.T.

24. Appropriate Therapy Leads to Lower Mortality in Gram-Negative Sepsis <0.001 49% (47-51%) 28% (22-32%) Total <0.001 29% (23-31%) 10% (0-13%) Non-fatal <0.001 67% (63-72%) 42% (39-45%) Ultimately fatal NS 85% (71-100%) 84% (80-86%) Rapidly fatal P-value Mortality without appropriate therapy Combined data (range) Mortality with appropriate therapy Combined data (range) Underlying Disease Bochud P-Y et al. Intensive Care Med 2001;27:S33-S48. C.Y.T.

25. Mortality Associated With Initial Inadequate Therapy In Critically Ill Patients With Serious Infections in the ICU 0% 20% 40% 60% 80% 100 % Luna, 1997 Ibrahim, 2000 Kollef, 1998 Kollef, 1999 Rello, 1997 Alvarez-Lerma,1996 Initial appropriate therapy Initial inadequate therapy *Mortality refers to crude or infection-related mortality Alvarez-Lerma F et al. Intensive Care Med 1996;22:387-394. Ibrahim EH et al. Chest 2000;118L146-155. Kollef MH et al. Chest 1999; 115:462-474 Kollef MH et al. Chest 1998;113:412-420. Luna CM et al. Chest 1997;111:676-685. Rello J et al. Am J Resp Crit Care Med 1997;156:196-200. Mortality* C.Y.T.

31. Spectrum of Potential Pathogens in Hospital-Acquired Pneumonia* Based on Severity of Illness Campbell GD et al. Am J Respir Crit Care Med 1996;153:1711-1725 * Excludes patients with immunosuppression. ** Includes severe HAP without risk factors (early onset) *** Severe HAP with risk factors (onset any time) or severe HAP without unusual risk factors (late onset) Mild-to-Moderate (With risk factors) Severe*** Core Organisms Enteric GNB Core Organisms, Plus Anaerobes Core Organisms , Plus P. aeruginosa (Non-pseudomonal) (recent abdominal • Enterobacter surgery; witnessed Acinetobacter • E. coli aspiration) species • Klebsiella • Proteus Consider MRSA • Serratia marcescens Haemophilus influenzae S. aureus (including MRSA if coma, head trauma, DM, renal failure) Methicillin-sensitive Legionella Staphylococcus aureus (high-dose steroids) Streptococcus pneumoniae P. aeruginosa (prolonged ICU, steroids, antibiotics) structural lung disease, Mild-to-Moderate (No unusual risks)** C.Y.T.

34. Risk Factors for Resistance in VAP Adapted from Trouillet J-L et al. Am J Respir Crit Care Med 1998;157:531-539. MRSA, P. aeruginosa , A. baumannii , S. maltophilia More sensitive bacteria than in Group 2 More resistant bacteria than in Group 3 Antibiotic-sensitive organisms (e.g., pneumococci, H. influenzae ) MV ≥7 days; prior use of antibiotics MV ≥7 days; no prior antibiotics MV <7 days; prior use of antibiotics MV <7 days; no prior antibiotics Group 4 Group 3 Group 2 Group 1 C.Y.T.

38. Resistant Pathogens Account for High Number of Bloodstream and Nosocomial Infections Kollef MH et al. Clin Inf Dis 2000;31(Suppl. 4):S131-S138. Coagulase-negative Staphylococci P= .001 0 10 20 30 40 50 Bloodstream infection Nosocomial pneumonia Urinary tract infection Invasive device present Percentage occurrence P. aeruginosa P= .002 A. baumannii P= .006 E. coli P= .023 C. albicans P= .009 Invasive device absent C.Y.T.

43. 抗生素的抗藥性 (ICU, 2004 NNIS Report)

44. 抗生素的抗藥性 (2004 NNIS Report)

48. Most Frequently Reported Pathogens from ICU Patients with Nosocomial Pneumonia 1. Pseudomonas aeruginosa 2. Staphylococcus aureus 3. Enterobacter spp. 4. Klebsiella pneumoniae 5. Acinetobacter spp. Richards MJ et al. Crit Care Med 1999; 887-892. C.Y.T.

55. Considerations for choosing empirical therapy  In vitro activity of drugs against likely pathogens  Local resistance burden  Pharmacologic and pharmacodynamic properities of antimicrobials  Safety and tolerability C.Y.T.

60. An Art in Medicine Balance An Evidence-Based Problem: Mortality with Inadequate Therapy A Theoretical Dilemma: Concern of Resistance with Broad-Spectrum Therapy Evans RS et al. N Engl J Med 1998;338:232-238. Gruson D et al. Am J Respir Crit Care Med 2000;162:837-843. Raymond DP et al. Crit Care Med 2001;29:1101-1108. ⋆ Clinical evidence showing lack of resistance with heterogeneous use of broad-spectrum therapy C.Y.T.

61. C.Y.T.

63. Thank you for your attention !