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Nosocomial Infections. Emergence of Antimicrobial Resistance. Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center. Impact of Antibiotic Restriction on Resistance Neurosurgical Intensive Care Unit in London. All antibiotics stopped.

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Nosocomial Infections

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nosocomial infections

Nosocomial Infections

Emergence of Antimicrobial Resistance

Mazen Kherallah, MD, FCCP

King Faisal Specialist Hospital & Research Center

impact of antibiotic restriction on resistance neurosurgical intensive care unit in london
Impact of Antibiotic Restriction on ResistanceNeurosurgical Intensive Care Unit in London

All antibiotics stopped

1968 1969 1970

Price. Lancet. 1970

possible explanation for decrease in infection rate
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
antimicrobial resistance a global problem
Antimicrobial Resistance:A Global Problem
  • ICAAC 1998
  • Antimicrobial Resistance Symposium: 200 attendees
  • Infectious disease physicians (25%), microbiologist (25%), other physicians, pharmacists, etc. (50%)
  • 80% agreed that antimicrobal resistance is increasing70% believed resistant pathogens cause greater mortality
Rates of Resistance Among Nosocomial Infections Reported in Intensive Care Patients, Comparison of 1999 (January-July) with Historical Data

January-July 1999


emerging pathogens
Emerging Pathogens
  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Methicillin-resistant Staphylococcus epidermitis (MRSE)
  • Vancomycin-resistant enterococci (VRE)
  • Vancomycin-intermediate Staphylococcus aureus (VISA)
  • Extended-spectrum beta-lactamase (ESBL)-producing gram-negative organisms
  • Multidrug-resistant Acinetobacter spp.
percentage of nosocomial staphylococcus aureus reported as resistant to methicillin by year
Percentage of Nosocomial Staphylococcus aureus Reported as Resistant to Methicillin, by year

National Nosocomial Infections Surveillance (NNIS), 1989-1998: system Data

secular trend in mrsa infections inspear 1990 1997
Secular Trend in MRSA InfectionsINSPEAR, 1990-1997

International Network for Surveillance and Prevention of Emerging

Antimicrobial Resistance (INSPEAR)

methicillin resistant staphylococcus aureus current status
Methicillin-Resistant Staphylococcus aureus:Current Status
  • Endemic beginning 1980 in hospitals
  • Increasing reports of community infections:
    • Pediatric outpatients in Chicago
    • Alaskan natives
    • 4 Pediatric deaths: MMWR 1998
epidemiology of vre
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
progression of vancomycin resistance enterococci
Progression of Vancomycin Resistance Enterococci

Mortone. WJ. Infect Control Hosp Epidemiol. 1998

NNIS Antimicrobial Resistance Surveillance Report 1999

risk factors for vre
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
Antibiotics and Colonization with VRE

Ostrowsky. Arch Intern Med. 1999

use of vancomycin in us and rate of vre
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)

enterococcal resistance by species
Enterococcal Resistance by Species

Jones. Diagn. Microbiol Infect Dis. 1998

outcome of enterococcus faecium bacteremia
Outcome of Enterococcus faecium Bacteremia

Stosor. Arch Intern Med. 1998

impact of formulary change on vre empiric therapy for febrile neutropenia
Impact of Formulary Change on VREEmpiric therapy for febrile neutropenia

Lisgaris. IDSA (abstract). 2000

prevention of gre therapy for febrile neutropenia
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


Phase 1 vs 2b (P<0.001)

Bradley. JAC. 1999

impact of cdc guidelines on endemic vre
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

emergence of vancmycin intermediate staphylococcus aureus visa in the world
Emergence of Vancmycin-Intermediate Staphylococcus aureus (VISA) in the World
  • First episode reported in Japan, 1996
  • Predicted risk factors:
    • MRSA colonization/infection
    • Frequent/sustained vancomycin exposure
  • Predicted high risk population
    • ESRD on hemodialysis
    • Long-term CVCs
    • Rehab/skilled nursing facility patients
    • Prolonged ICU stay
extended spectrum lactamases esbls
Extended Spectrum -lactamasesESBLs
  • 1983: first reported in Europe
  • 1988:: reported in the United States
  • 1990’s: increased prevalence globally:
    • ICU’s
    • Acute care
    • Extended care
  • 2000: Problematic nosocomial pathogen
extended spectrum lactamases esbls1
Extended Spectrum -lactamasesESBLs
  • 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
klebsiella pneumoniae resistance to third generation cephalosporins cdc
Klebsiella pneumoniaeResistance to third-generation cephalosporinsCDC

Fridkin and Gaynes. Clin Chest Med. 1999

K. pneumoniae Resistant to Extended-Spectrum -lactam (ESBL) at NNISEvidence of Inter-hospital Transmission

Mannel DL, et al. Infect Control Hosp Epidemiolo 1997

emergence of carbapenem resistant acinetobacter spp
Emergence of Carbapenem-resistant 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
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
Antimicrobial Susceptibility of 233 Acinetobacter spp., 15 Hospital, Brooklyn, New York

VM Manikal et al. CID. 2000

control measures
Control Measures
  • Barrier precautions
  • Oxyamino beta-lactam restriction
  • Selective bowel decontamination
antimicrobial utilization and resistance
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 resistance1
Antimicrobial Utilization and Resistance

Piperacillin/tazobactam resistant

Smith. Pharmacotherapy 1999

impact of formulary changes on mrsa and ceftazidime resistant k pneumoniae
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

impact of a rotating empiric antibiotic schedule on infectious mortality in an intensive care unit
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 unit1
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

  • Epidemiology of resistance in gram-negative and gram-positive organisms is complex, and is influenced, in part, by selective antimicrobial pressure
  • Control measures for emerging resistance include:
    • Traditional infection control measures: contact isolation
conclusion judicious use of antimicrobial
ConclusionJudicious Use of Antimicrobial
  • Decrease cephalosporin use
  • Increase extended-spectrum penicillin/beta-lactamase inhibitor use
  • Limit carbapenem and vancomycin use to desired therapy