Strategies in the Selection of Antibiotic Therapy in the ICU Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center
Scope of the Problem Inadequate Initial Antibiotic Therapy Bacterial Resistance
Infection Distribution in Adult ICU’s Major Types of Infection (NNIS data, 1992 -1997)
Nosocomial Infection Richards MJ et al, CCM. 1999; 27: 887 -882
NNIS Richards MJ et al, CCM. 1999; 27: 887 -882
Pathogens Most Frequently associated with Nosocomial Pneumonia in the ICU
Inadequate Initial Antibiotic Therapy
Initial Inadequate Therapy
Mortality Associated with Initial Inadequate Therapy
Resistant Pathogens, Inadequate Treatment and Mortality (BSI) Ibrahim EH, et al. Chest 2000; 118: 145 -155
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
Infection Classification Kollef MH, et al chest. February 1999; 115(2): 462 -474
Cohort of Infected Patients and Inadequate Therapy Kollef MH, et al chest. February 1999; 115(2): 462 -474
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
Clinical Outcomes Kollef MH, et al chest. February 1999; 115(2): 462 -474
Hospital Mortality of Infected Patients P<0. 001 Kollef MH, et al chest. February 1999; 115(2): 462 -474
Reduce Inappropriate Initial Antimicrobial Therapy ► Guidelines ► Broad spectrum and combination antibiotics ► ID consultation ► Automated antibiotic consultant ► More selective and sensitive diagnostic methods
Clinical Guidelines for the Treatment of Ventilator Associated Pneumonia ► Prospective study: 50 patients were evaluated in the before group and 52 in the after group ► Administration of vancomycin/imipenem/ciprofloxacin within 12 hours of clinical diagnosis ► Antibiotic modification after 24 -48 hrs ► Seven-day course of therapy (>7 days if symptoms and signs are persisted) Ibrahim EH et al. Crit Care Med, 2001; 29: 1109 -1115
Clinical Guidelines for the Treatment of Ventilator Associated Pneumonia Ibrahim EH et al. Crit Care Med, 2001; 29: 1109 -1115
Automated Antibiotic Consultant Evans Arch Int Med 1994
Broad-Spectrum and Combination Antibiotics Trouillet et al. Am J Res Crit Care Med. 1998; 157: 531 -539
ID Consultation Byl B. Clin Inf Dis; 1989
Emergent Bacterial Resistance
Impact of Antibiotic Restriction on Resistance Neurosurgical Intensive Care Unit in London All antibiotics stopped 1968 1969 1970 Price. Lancet. 1970
Decrease in Hospital-acquired ICU Infection Rates, NNIS, 1990 -1999
Possible Explanation for Decrease in Infection Rate ► Efforts to prevent infections: new research findings, prevention guidelines ► Shift of health care from hospital-based care ► True decrease secondary to adhesion to infection control policies
Rates of Resistance Among Nosocomial Infections Reported in Intensive Care Patients, Comparison of 1999 (January-July) with Historical Data January-July 1999 1993 -1998
Emerging Pathogens ► Methicillin-resistant Staphylococcus aureus (MRSA) epidermitis (MRSE) ► Vancomycin-resistant enterococci (VRE) ► Vancomycin-intermediate Staphylococcus aureus (VISA) ► Extended-spectrum beta-lactamase (ESBL)-producing gram-negative organisms
Antibacterial Resistance in Nosocomial Infections Gram-Negative Pathogens Fridkin and Gaynes. Clin Chest Med. 1999: 20: 302 -315
Antibacterial Resistance in Nosocomial Infections Gram-Positive Pathogens Fridkin and Gaynes. Clin Chest Med. 1999: 20: 302 -315
Methicillin Resistant Staphylococci by setting Fridkin. Clin Infect Dis. 1999
Vancomycin-resistant Staphylococcus aureus ► June 2202 - First case of VRSA isolated from a swab obtained from a catheter exit site ► The isolate was resistant to: § Oxacillin (MIC >16 µg/ml) § Vancomycin (MIC >128 µg/ml) ► The isolate contained: § The oxacillin-resistant gene mec. A § The van. A vancomycin resistant gene from enterococci CDC MMWR. 2002; 51: 565 -567
Epidemiology of VRE ► Present in all 50 states in the United States ► Number of isolated continues to grow ► Recognized in Europe, Japan, Central and South America ► Resistance to alternate antibiotic therapy continues to be a problem
Risk Factors for VRE ► Prior broad spectrum antibiotics (especially cephalosporins and vancomycin) ► Prolonged hospitalization ► Immunocompromised host ► Neutropenia ► Admission to an intensive care unit ► Renal failure requiring dialysis Noskin. J Lab Clin Med. 1997
Antibiotics and Colonization with VRE Ostrowsky. Arch Intern Med. 1999
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)
Independent Predictors of Vancomycin. Resistant Enterococci in Adult Intensive Care Units NNIS
Enterococcal Resistance by Species Jones. Diagn. Microbiol Infect Dis. 1998
Outcome of Enterococcus faecium Bacteremia Stosor. Arch Intern Med. 1998
Extended Spectrum lactamases ESBLs ► ESBL inactivates oxyamino beta-lactams and fourth-generation cephalosporins (to some extent) and aztreonam ► Large plasmids encoding multiple antibiotic resistance determinants including aminoglycoside modifying enzymes ► Strains producing ESBL are typically sensitive to cephamycins and carbapenems ► Common ESBL-producers: K. pneumoniae, and less common other Enterobactericae
K. pneumoniae Resistant to Extended. Spectrum -lactam (ESBL) at NNIS Evidence of Inter-hospital Transmission Mannel DL, et al. Infect Control Hosp Epidemiolo 1997
Emergence of Carbapenemresistant Acinetobacter spp. ► Frequent use of aminoglycosides, fluroquinolones, ureidopenicillins and third generation cephalosporins ► Reported from South America, Europe, Far East, Middle East, and United States ► Numerous outbreaks (some strains susceptible only to polymyxin B) ► High mortality rates ► Endemic in some hospitals
Endemic Carbapenem-Resistant Acinetobacter spp. In Brooklyn, New York ► ► ► 15 hospitals November 1997, all aerobic bacteria collected Acinetobacter spp. (233) accounted for 10% of the gram negative bacilli Carbapenem resistance ranged from 0 -100% 10% of isolated were susceptible only to polymyxin Risk factors § Use of third generation cephalosporins plus aztreonam § Environment and healthcare worker hands contamination documented § PFGE documented inter- and intra-hospital spread VM Manikal et al. CID. 2000
Antimicrobial Susceptibility of 233 Acinetobacter spp. , 15 Hospital, Brooklyn, New York VM Manikal et al. CID. 2000
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
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
Impact of Formulary Change on VRE Empiric therapy for febrile neutropenia Lisgaris. IDSA (abstract). 2000
Prevention of GRE Therapy for Febrile Neutropenia ► Purpose: reduce glycopeptide resistant enterococci (GRE) ► Situation: 50% colonization rate in oncology units ► Methods: § Phase 1: no intervention (ceftazidime) § Phase 2 a and 2 b: replace ceftazidime with piperacillin/tazobactam § Phase 3: return to ceftazidime Bradley. JAC. 1999
Results Phase 1 vs 2 b (P<0. 001) Bradley. JAC. 1999
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
Antimicrobial Utilization and Resistance Piperacillin/tazobactam resistant Smith. Pharmacotherapy 1999
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
Ceftazidime Resistant K. pneumoniae Cleveland VA Medical Center
Impact of a Rotating Empiric Antibiotic Schedule on Infectious Mortality in an Intensive Care Unit Raymond DP. Crit Care Med 01 -Jun-2001, 29(6); 1101 -8
Impact of a Rotating Empiric Antibiotic Schedule on Infectious Mortality in an Intensive Care Unit Raymond DP. Crit Care Med 01 -Jun-2001, 29(6); 1101 -8
Short Course Antibiotic Therapy Hospital Acquired Pneumonia Clinical Pulmonary Infection Score (CPIS) <6 >6 Antibiotics 10 -21 days Ciprofloxacin 3 days Antibiotics 10 -21 days Reevaluate CPIS at 3 days <6 D/C >6 treat as pneumonia Singh N, et al. Am J Resp Crit Care Med. 2000; 162: 505 -511
Short Course Antibiotic Therapy Hospital Acquired Pneumonia Singh N, et al. Am J Resp Crit Care Med. 2000; 162: 505 -511
In Conclusion:
Reduce Inappropriate Initial Antimicrobial Therapy ► Guidelines and goal directed protocols ► Broad spectrum and combination antibiotics ► ID consultation ► Automated antibiotic consultant! ► More selective and sensitive diagnostic methods
Efforts to Decrease the Rate of Emergent Antimicrobial Resistance CDC guidelines and barrier precautions ► Antibiotic restriction and appropriate utilization: § Decrease cephalosporin use § Increase extended-spectrum penicillin/betalactamase inhibitor use § Limit carbapenem and vancomycin use to desired therapy ► Selective bowel decontamination ► Rotation antibiotics ► Short course antibiotic course: HAP ►
Conclusion Judicious Use of Antimicrobial ► Decrease cephalosporin use ► Increase extended-spectrum penicillin/beta-lactamase inhibitor use ► Limit carbapenem and vancomycin use to desired therapy
Handwashing compared to Alcohol Hand
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