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Resistant GramNegative Bacilli ESBLs and Other Bad Bugs

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Still common in their nich s; level ... Hyle EP Arch Int Med 2005 (HUP) ... Hyle EP Arch Int Med 2005 (HUP) Resistant GNB. Clinical Significance. NNIS data ... – PowerPoint PPT presentation

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Title: Resistant GramNegative Bacilli ESBLs and Other Bad Bugs


1
Resistant Gram-Negative Bacilli ESBLs and Other
Bad Bugs
  • David P. Dooley, FACP
  • UTHSC-San Antonio
  • Audie Murphy VA Hospital
  • San Antonio, TX

2
Resistant GNB The Problem
  • Still common in their nichés level prevalance of
    GNBs, but resistance rising

3
Results of intensive care unit surveillance
revealing percentages of gram-positive (Gram Pos)
and gram-negative (Gram Neg) pathogens associated
with pneumonia, urinary tract infection (UTI),
surgical site infection (SSI), and bloodstream
infection (BSI)National Nosocomial Infections
Surveillance system, 19862003.
4
Results of intensive care unit surveillance for
the proportion of selected gram-negative
organisms reported for pneumonia from
the National Nosocomial Infections Surveillance
system, 19862003. Gaynes R CID 2005 (CDC)
5
Resistant GNRs
Prevalence of isolates of multidrug-resistant
gram-negative bacilli recovered within the first
48 h after admission to the hospital, by species.
Only 1 isolate per patient per year was included
in the study.
Pop-Vicas, Clin Inf Dis 401794 2005 (MGH)
6
Results of intensive care unit surveillance
revealing rates of antimicrobial resistance to
third-generation cephalosporins among Klebsiella
pneumoniae isolates (which includes isolates that
were either intermediately susceptible or
resistant) and Escherichia coli isolatesNational
Nosocomial Infections Surveillance system,
19862003. Gaynes R CID 2005 (CDC)
7
INCIDENCE RATES OF MULTIDRUG-RESISTANT BACTERIA
PER 100 ADMISSIONS STAPHYLOCOCCUS AUREUS (LINE
WITH BLACK DIAMONDS), PSEUDOMONAS AERUGINOSA
(LINE WITH WHITE DIAMONDS), ENTEROBACTERIACEAE
(LINE WITH BLACK BOXES), AND ACINETOBACTER
BAUMANNII (LINE WITH WHITE BOXES).
Lepelletier D ICHE 2004--Nantes
8
Resistant GNB The Problem
  • High mortality
  • Narrowing therapeutic options
  • Down to carbapenems, polymixin B

9
New antibacterial agents approved in the United
States, 19832002, per 5-year period.
Spellberg B et al. Clin Inf Dis 2004
10
Resistant GNB The Problem
  • Hard to detect may be in your building for
    months/years before you get worried
  • Not sexy no media exposure
  • How to compete with alarms about MRSA?

11
Resistant GNB
  • Organisms of concern
  • Pseudomonas aeruginosa
  • Acinetobacter baumannii
  • Enterobacteriaceae
  • Klebsiella pneumoniae
  • Enterobacter spp. (esp cloacae)
  • E. coli
  • Serratia marcescens

12
Sites of infection with extended-spectrum
ß-lactamaseproducing Escherichia coli and
Klebsiella species 187 patients at HUP, over 5 y
Hyle EP Arch Int Med 2005 (HUP)
13
Resistant GNB Clinical Significance
  • High mortality, especially with pneumonia or BSIs
  • Clear effect of delay in appropriate therapy on
    survival
  • 40-100 mortality when treating apparently
    susceptible deep infections with Klebsiella with
    cephalosporins

14
Delay in initial antimicrobial therapy and
mortality.
Hyle EP Arch Int Med 2005 (HUP)
15
Resistant GNB Clinical Significance
  • NNIS data
  • 20 of ICU Klebsiella isolates are resistant to
    30 cephalosporins
  • 30 of ICU Enterobacter isolates similar
  • 6 of E. coli isolates similar
  • (Netherlands lt1 of Klebsiella with ESBLs!)

16
Resistant GNB Epidemiology
  • Risks for acquisition No surprises
  • Current and previous abx Tx
  • Older patient (gt60 y)
  • ICU stay prolonged ICU stay
  • IV catheters tubes of every kind
  • NH/LTCF denizen (1/2 colonized with ESBLs!)
  • H2 receptor blockers (Zantac et al)
  • Chronic liver/renal disease

17
Safdar N, Maki DG, Ann Int Med 2002136834
18
Resistant GNB Epidemiology
  • Risk of deep infection gtgt if previously colonized
    (40 fold)
  • 15 of colonized patients go on to invasive
    infection
  • Rare community-acquired

19
Resistant GNB Epidemiology when/how acquired?
  • Horizontal transfer vs endogenous source
  • Unlike MRSA, VRE---overwhelmingly horizontal
    transfer
  • Endogenous
  • Enterobacteriaceae seldom spontaneously
    resistant Pseudomonas not cultured from normal
    individuals (Acinetobacter /-)
  • But resistance in same clone emerges commonly
    under antibiotic pressure

20
Resistant GNB Epidemiology when/how acquired?
  • Clearly some horizontal transfer though
  • How?
  • 5 (ltlt MRSA) of area around bedside of colonized
    patients are colonized with resistant GNBs---but
    theyre there environmental reservoir
  • (Clearly documented point source outbreaks)
  • Large (undetermined) percentage of colonization
    occurs through HCWs hands (esp Klebsiella and
    Acinetobacter)

21
PERCENTAGE OF HAND IMPRINT CULTURES YIELDING
PATHOGENS AFTER CONTACT WITH ENVIRONMENTAL
SURFACES NEAR PATIENTS IN OCCUPIED PATIENT ROOMS
OR IN ROOMS THAT HAD BEEN CLEANED AFTER PATIENT
DISCHARGE.
Bhalla A ICHE 2004 (Cleveland)
22
Larson EL et al Ped Crit Care Med 2005
23
Distribution of infant and nurse clones
identified as unique strains, strains shared
between nurses and infants, and strains shared
between nurses or among infants.
Waters V, Clin Inf Dis 2004 (Columbia)
24
Resistant GNB Basis of Resistance
  • Pseudomonas aeruginosa, Acinetobacter spp.
    Intrinsically resistant through multiple
    mechanisms
  • ß-lactamasesmany possible
  • Aminoglycoside modifying enzymes
  • Porin mutations, with abx exclusion
  • Efflux pumps up and running
  • Topoisomerases for FQs

25
Resistant GNB Basis of Resistance
  • Enterobacteriaceae ß-lactamases rising
  • 1960sroutine enzymes (TEM 1, SHV 1)
    ampicillin, Keflex resistant
  • 1980smutations extended spectrumDNA encoded
    on plasmids, jump to other GNBs easily
  • Active against 30 cephalosporins, aztreonam
  • Not active (stay susceptible) against cefoxitin,
    cefotetan, and ß-lactamase inhibitors (Zosyn,
    Augmentin, Unasyn)
  • Currently gt100 ESBLs recognized

26
Resistant GNB Basis of Resistance Example
  • Klebsiella pneumoniae, old TEM 1
  • Amp R
  • Keflex R
  • Cefoxitin S
  • Cefotaxime/ceftriaxone S
  • Ceftazidime S
  • Cefipime S
  • Zosyn S
  • Cipro S
  • Aminoglycoside S
  • Bactrim S

27
Resistant GNB Basis of Resistance Example
  • Klebsiella pneumoniae, old TEM 1 new ESBL
  • Amp R R
  • Keflex R R
  • Cefoxitin S S
  • Cefotaxime/ceftriaxone S R
  • Ceftazidime S R
  • Cefipime S (S)
  • Zosyn S S
  • Cipro S (S)
  • Aminoglycoside S (S)
  • Bactrim S (S)

28
Resistant GNB Basis of Resistance
  • Amp C ßlactamases newer, broader R
  • Chromosomal dont jump so much
  • Mostly on Enterobacters rare Kleb
  • Do cause R to cefoxitin, and ßlactamase
    inhibitor combinations

29
Resistant GNB Basis of Resistance Example
  • Klebsiella pneumoniae, old TEM 1 new ESBL Amp-C
  • Amp R R R
  • Keflex R R R
  • Cefoxitin S S R
  • Cefotaxime/ceftriaxone S R R
  • Ceftazidime S R R
  • Cefipime S (S) (S)
  • Zosyn S S R
  • Cipro S (S) (S)
  • Aminoglycoside S (S) (S)
  • Bactrim S (S) (S)

30
Resistant GNB Basis of Resistance
  • ESBLs and Amp-C ßlactamases are inoculum
    dependent
  • Usual tests are at low inoculum may look S
  • In vivo, high loads of bugs common clinical
    failures of the S abx is common
  • Requires special testing techniques
  • If not performed, ESBL/Amp-C bugs may look S but
    your patients are dying
  • CLSI recommends specific testing if ESBL or Amp
    C are found, trust NO and treat with NO ß-lactam
    except carbapenem (imipenem, meropenem, ertapenem)

31
Resistant GNB Deceptive Susceptibility Testing
ESBLs May Look Sensitive
  • Klebsiella pneumoniae
  • Amp R
  • Keflex R
  • Cefoxitin S
  • Cefotaxime/ceftriaxone S
  • Ceftazidime (S)
  • Cefipime S
  • Zosyn S
  • Cipro S
  • Aminoglycoside S
  • Bactrim S

32
Resistant GNB Deceptive Susceptibility Testing
Amp-Cs May Look Sensitive Early On
  • Enterobacter spp. Amp-C early Amp C 3-10 d
    later
  • Amp R R
  • Keflex R R
  • Cefoxitin S R
  • Cefotaxime/ceftriaxone S R
  • Ceftazidime S R
  • Cefipime S (S)
  • Zosyn S R
  • Cipro (S) (S)
  • Aminoglycoside (S) (S)
  • Bactrim (S) (S)

33
Double-disk susceptibility test for ESBLs, this
time in Enterobacter cloacae. AMC (center)
clavulanic acid FEP cefepime CAZ
ceftazidime CXT cefotaxime CRO ceftriaxone
34
Resistant GNB Treatment
  • Must pick adequate coverage immediately (reviewed
    already).
  • Greater survival differences in under-treated
    resistant GNBs than even under-treated MRSA
  • Patients at risk should receive broader coverage
  • Carbapenems /- double GNB coverage

35
Rahal et al Clin Inf Dis 200234501
Squeezing the balloon. Evolution and control
of antibiotic resistance among gram-negative
bacilli at New York Hospital Queens. ICU,
intensive care unit.
36
Resistant GNB Infection Control Issues
  • Prevention of transmission of resistant
    Staphylococcus aureus and Enterococcus
    specifically addressed in 2003 SHEA guideline
  • Call for active surveillance cultures, based on
  • Recognition that colonization precedes infection
  • Response with barrier precautions works to reduce
    clinical infections
  • Response if wait till clinical cultures return
    positive is less impressive (vs no help)

Muto CA ICHE 200324362
37
Resistant GNB Infection Control Issues
  • HICPAC guidelines address all MDROs
  • Call for measured response
  • Active surveillance (rectal cultures in case of
    ESBLs) if institution has a problem
  • Otherwise, adjust level of surveillance/recognitio
    n to overall need, or focus on geographic areas
    in house (e.g., ICUs)
  • Decisions made on basis of your institutions
    amount of problem, resources, administrations
    interest

Siegel et al www.cdc.gov/ncidod/dhqp/pdf/ar/mdr
oGuideline2006.pdf
Discussion at Jackson M et al AJIC 200432504
38
Resistant GNB Infection Control Issues
  • Other components of infection control
  • Antibiotic stewardship program
  • Probably as or more important here than for other
    MDROs
  • Carbapenems for empirical therapy avoid
    ceftazidime avoid 30 cephalosporins in general
    (Zosyn maybe helfpul)
  • Contact precautions interrupt environmental
    risk
  • Determine clonality if available (also, ? Point
    source?)

Good evidence intervention works
39
Resistant GNB Infection Control Issues
  • Hand hygiene
  • Cohorting patients, cohorting staff
  • Good staffing ratios

Good evidence intervention works
40
Resistant GNB Infection Control Issues
  • Cautions
  • Contact precaution data is not usually in
    isolation
  • Active surveillance costs
  • Money
  • Time
  • Effort
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