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Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center

Inadequate Empiric Antibiotic Therapy. Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center. Terms. Infection SIRS Bacteremia and BSI Sepsis Severe sepsis. Sepsis Syndromes 1992: SCCM/ACCP. Parasite. Severe Sepsis. Virus. SIRS. Infection. Sepsis. Fungus.

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Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center

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  1. Inadequate Empiric Antibiotic Therapy Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center

  2. Terms • Infection • SIRS • Bacteremia and BSI • Sepsis • Severe sepsis

  3. Sepsis Syndromes1992: SCCM/ACCP Parasite Severe Sepsis Virus SIRS Infection Sepsis Fungus Severe SIRS Trauma Shock Bacteria BSI Burns

  4. A clinical response arising from a • nonspecific insult, including 2 • of the following: • Temperature 38oC or 36oC • HR 90 beats/min • Respirations 20/min • WBC count 12,000/mm3or 4,000/mm3 or >10% immature • neutrophils SIRS due to Infection The Sepsis Continuum Infection/Trauma Sepsis Severe Sepsis SIRS SIRS = systemic inflammatory response syndrome. Bone et al. Chest. 1992;101:1644.

  5. Shock The Sepsis Continuum Infection/Trauma Sepsis Severe Sepsis SIRS • Sepsis with 1 sign of organ dysfunction *Cardiovascular (refractory hypotension) *Renal *Respiratory *Hepatic *Hematologic *CNS *Unexplained metabolic acidosis SIRS = systemic inflammatory response syndrome. Bone et al. Chest. 1992;101:1644.

  6. Sepsis: A Complex ClinicalChallenge Infection/Trauma Sepsis Severe Sepsis SIRS • High mortality rate (35%-45%) • Heterogeneous patient population • Unpredictable disease progression • Unclear etiology and pathogenesis Wheeler and Bernard. N Engl J Med. 1999;340:207.

  7. Sepsis: A Deadly Healthcare Challenge Study Condition Mortality Rate (N) Brun-Buisson, 1995* Abraham, 1997† Natanson, 1998‡ Friedman, 1998§ Severe sepsis Severe sepsis Septic shock Severe sepsis/septic shock Septic shock 56%-60% (1052) 36% (78) 42% (62) 38% (4356) 49.7% (10,694) *Prospective survey, 28-day mortality; †Randomized placebo-controlled trial, 28-day mortality; ‡Analysis of placebo arms in 21 recent clinical trials; §Analysis of 131 studies. Brun-Buisson et al. JAMA. 1995;274:968; Abraham et al. JAMA. 1997;277:1531; Natanson et al. Crit Care Med. 1998:26:1927; Friedman et al. Crit Care Med. 1998;26:2078.

  8. Severe Sepsis: A Significant Healthcare Challenge †Angus DC et al. Crit Care Med. 2001 . ‡Sands KE et al. JAMA. 1997;278:234-40. §Zeni F et al. Crit Care Med. 1997;1095-100.

  9. Reduction of Mortality • Infection specific treatment • Appropriate antimicrobials • Sepsis specific treatment • Drotrecogin alpha: activated protein C • Supportive treatment • Early goal directed therapy • Intensive insulin therapy • Low tidal volume ventilation • Low dose steroids

  10. Empiric Antimicrobial Regimen • Initial antibiotic regimen chosen for suspected infection based on clinical presentation and local epidemiological data, pending the results of obtained cultures. • When culture results are obtained: • Appropriate initial regimen is the regimen which included antibiotics turned out to be covering the isolated organism(s) • Inappropriate initial regimen is the regimen which did not include antibiotic(s) covering the isolated organism(s), and change of antibiotic is necessary to cover those organisms

  11. Inappropriate Initial Antimicrobial Therapy 430 60 65 100

  12. Mortality Associated with Initial Inadequate Therapy

  13. Inadequate Treatment and Mortality: (BSI) Resistant Pathogens Ibrahim EH, et al. Chest 2000;118:145-155

  14. Inadequate Antimicrobial Therapy • 2000 consecutive MICU/SICU patients • 655 (25.8%) with infections • 169 (8.5%) with inadequate therapy Kollef MH, et al chest. February 1999;115(2):462-474

  15. Infection Classification Kollef MH, et al chest. February 1999;115(2):462-474

  16. Cohort of Infected Patients and Inadequate Therapy Kollef MH, et al chest. February 1999;115(2):462-474

  17. Most Common Pathogens • Inadequate therapy (n=169) • P. aeruginosa: 53 • MRSA: 45 • VRE: 13 • Adequate therapy (n=486) • Escherchia coli: 76 • MSSA: 88 Kollef MH, et al chest. February 1999;115(2):462-474

  18. Clinical Outcomes Kollef MH, et al chest. February 1999;115(2):462-474

  19. Hospital Mortality of Infected Patients P<0.001 Kollef MH, et al chest. February 1999;115(2):462-474

  20. Inappropriate Empiric Antibiotic Therapy: KFSHRC-Jeddah Total of 105 patients with clinically significant, microbiologically documented infection

  21. Inappropriate Initial Antimicrobial Therapy 430 60 65 100 105

  22. Inappropriateness based on Infection Setting: KFSHRC-Jeddah KFSHRC-Jeddah, QM data 2002

  23. Inappropriateness as per Site of Infection KFSHRC-Jeddah, TQM data 2002

  24. Based on Previous Antibiotic Use KFSHRC-Jeddah, TQM data 2002

  25. Inappropriate Empiric Antibiotic Therapy: KFSHRC-Jeddah Total of 27 patients with hospital acquired infections and previously on antibiotics KFSHRC-Jeddah, TQM data 2002

  26. Inappropriate Coverage as per Organism 3 3 11 10 6 18 23 KFSHRC-Jeddah, TQM data 2002

  27. Reasons for Inappropriateness KFSHRC-Jeddah, TQM data 2002

  28. Reasons for Inappropriateness Bacterial Resistance KFSHRC-Jeddah, 2002

  29. Rates of Resistance Among Nosocomial Infections Reported in Intensive Care Patients, Comparison of 1999 (January-July) with Historical Data January-July 1999 1993-1998

  30. Antibacterial Resistance in Nosocomial InfectionsGram-Negative Pathogens Fridkin and Gaynes. Clin Chest Med. 1999:20:302-315

  31. Antibacterial Resistance in Nosocomial InfectionsGram-Positive Pathogens Fridkin and Gaynes. Clin Chest Med. 1999:20:302-315

  32. Methicillin Resistant Staphylococci by setting Fridkin. Clin Infect Dis.1999

  33. Use of Vancomycin in US and Rate of VRE Kirsl et al. Historical usage of vancomycin. Antimicrob Agent Chemo 1998 National Nosocomial Infection Surveillance System (CDC)

  34. Enterococcal Resistance by Species Jones. Diagn. Microbiol Infect Dis. 1998

  35. Independent Predictors of Vancomycin-Resistant Enterococci in Adult Intensive Care Units NNIS

  36. Outcome of Enterococcus faecium Bacteremia Stosor. Arch Intern Med. 1998

  37. Reduce Inappropriate Initial Antimicrobial Therapy • Efforts to reduce rate of resistance • Guidelines • Broad spectrum and combination antibiotics • ID consultation • Automated antibiotic consultant • More selective and sensitive diagnostic methods

  38. Efforts to Decrease the Rate of Emergent Antimicrobial Resistance • CDC guidelines and barrier precautions • Antibiotic restriction • Selective bowel decontamination • Rotation antibiotics • Short course antibiotic course

  39. Impact of CDC Guidelines on Endemic VRE M. Montecalvo et al. Ann Int Med. 1999 J Morris et al. Ann Int Med. 1995 E Jochimsen et al. ICHE 1999

  40. Impact of Formulary Change on VREEmpiric therapy for febrile neutropenia Lisgaris. IDSA (abstract). 2000

  41. Prevention of GRETherapy for Febrile Neutropenia • Purpose: reduce glycopeptide resistant enterococci (GRE) • Situation: 50% colonization rate in oncology units • Methods: • Phase 1: no intervention (ceftazidime) • Phase 2a and 2b: replace ceftazidime with piperacillin/tazobactam • Phase 3: return to ceftazidime Bradley. JAC. 1999

  42. Results Phase 1 vs 2b (P<0.001) Bradley. JAC. 1999

  43. Antimicrobial Utilization and Resistance • Interdisciplinary team in Indianapolis to control resistant organisms • Interventions: • Reduce third generation cephalosporin use • Reduce imipenem use • Encourage use of ampicillin/sulbactam and piperacillin/tazobactam • Enhance compliance with infection control • Education regarding antimicrobial resistance

  44. Antimicrobial Utilization and Resistance Piperacillin/tazobactam resistant Smith. Pharmacotherapy 1999

  45. Impact of Formulary Changes on MRSA and Ceftazidime Resistant K. Pneumoniae • Reduce usage of cephalosporins, imipenem, clindamycin and vancomycin • Increased use of -lactam/-lactamase inhibitors Landman. Clin. Infect Dis. 1999

  46. Ceftazidime Resistant K. pneumoniaeCleveland VA Medical Center

  47. Reduce Inappropriate Initial Antimicrobial Therapy • Efforts to reduce rate of resistance • Guidelines • Broad spectrum and combination antibiotics • ID consultation • Automated antibiotic consultant • More selective and sensitive diagnostic methods

  48. Blood Stream Infections KFSHRC-Jeddah: Infection Control Data 2002

  49. Nosocomial Pneumonia KFSHRC-Jeddah: Infection Control Data 2002

  50. Urinary Tract Infection KFSHRC-Jeddah: Infection Control Data 2002

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