Slide 1

Report
Pseudomonas: Microbiologic and
Clinical Features
T. Mazzulli, MD, FRCPC, FACP
Microbiologist and Infectious Diseases
Consultant
Mount Sinai Hospital/UHN
Objectives
Review the current epidemiology of
antimicrobial resistance of key
bacterial pathogens
Discuss the mechanism of
resistance, cross-resistance and coresistance and laboratory detection
Review recommendations for
treatment and control of multi-drug
resistant pathogens
Microbiology
Family Pseudomonadaceae
– Aerobic, non-spore forming Gram negative straight or
slightly curved rod (1 to 3 um in length), polar flagella
– Non-fermenters
– Catalase and oxidase positive
– Morphologic characteristics on lab media:
Production of pigments:
– Soluble blue-coloured phenazine pigment called pyocyanin)
– Some strains produce red or black colonies due to pigments
termed pyorubin and pyomelanin, respectively
– P. aerugnosa produces pyoverdin (diffusible yellow-green to
yellow-brown pigment) which, when produced with pyocyanin
gives rise to green-blue colonies on solid media
– Term ‘aeruginosa” stems from green-blue hue
Microbiology
Term Pseudo = “false”; monas = “single unit”
Term ‘aeruginosa” stems from green-blue hue
Pseudomonas are classified as strict aerobes
but some exceptions:
– May use nitrate
– Biofilm formation
Microbiology
Pseudomonads classified into five rRNA
homology groups:
– Pseudomonas (sensu stricto)
– Burkholderia species
– Comamonas, Acidovorax, and Hydrogenophaga
genera
– Brevundimonas species
– Stenotrophomonas and Xanthomonas genera
Genus Pseudomonas contains over 160
species but only 12 are clinically relevant
Microbiology
P. aeruginosa is the type species and may
have highly varied morphology
Typical colonies may appear to spread over
the plate, lie flat with a metallic sheen and
frequently produce a gelatinous or “slimy”
appearance
Most strains produce characteristic
‘grapelike’ or ‘corn taco-like’ odor
P. aeruginosa on blood agar
Non-Lactose
Fermenter
Lactose
Fermenter
MacConkey Agar
P. aeruginosa
Mucoid P. aeruginosa
MacConkey Agar
Epidemiology and Clinical Aspects of
P. aeruginosa
Epidemiology and Transmission
Natural habitat:
– Temperature between 4 to 36oC (can survive up to
42oC)
– Found throughout nature in moist environment
(hydrophilic) (e.g. sink drains, vegetables, river water,
antiseptic solutions, mineral water, etc.)
– P. aeruginosa rarely colonizes healthy humans
Normal skin does not support P. aeruginosa colonization
(unlike burned skin)
– Acquisition is from the environment, but occasionally
can be from patient-to-patient spread
Range of clinical infections caused by P.
aeruginosa
P. aeruginosa is an opportunistic infection:
– Individuals with normal host defenses are not at risk
for serious infection with P. aeruginosa
Those at risk for serious infections include:
– Profoundly depressed circulating neutrophil count
(e.g. cancer chemotherapy)
– Thermal burns
– Patients on mechanical ventilation
– Cystic fibrosis patients
Range of clinical infections caused by P.
aeruginosa
Immunocompetent Host:
– Most common cause of osteochondritis of dorsum of foot
following puncture wounds (running shoes)
– Hot tub folliculitis
– Swimmer’s ear
– Conjunctivitis in contact lens users (poor hygiene or if lenses are
worn for extended periods)
Other Hosts:
–
–
–
–
–
–
Malignant otitis externa in diabetics
Meningitis post trauma or surgery
Sepsis and meningitis in newborns
Endocarditis or osteomyelitis in IVDUs
Community-acquired pneumonia in pts with bronchiectasis
UTI in patients with urinary tract abnormalitis
Number of isolates (one per patient)
Hospital-acquired gram negative organisms
Distribution in the ICU, 2004-2007
100
90
80
70
60
50
40
30
20
10
0
Other
Serratia
Acinetobacter
Stenotrophomonas
Enterobacter/citrobacter
E. coli
Klebsiella spp.
P. aeruginosa
2005
2006
2007
Bacterial Infections in the ICU:
Organism Distribution in North America
SENTRY: 2001
24-36 medical centers in N.A., n = 1321
Staphylococcus aureus
Pseudomonas aeruginosa
Escherichia coli
Klebsiella species
Enterococcus species
Coagulase negative staph
Enterobacter species
Acinetobacter species
Serratia species
Stenotrphomonas maltophilia
24.1
12.2
10.1
8.9
7.2
7.0
7.0
4.0
3.0
3.0
Jones, Sem Resp Crit Care Med, 2003
Incidence of Pathogens from ICUs in Canada
(87 hospitals sites): 2000 to 2002
Organism
S. aureus
Coag. Neg Staphylococcus
Enterococcus spp.
E. coli
P. aeruginosa
K. pneumoniae
Enterobacter cloacae
Enterobacteriaceae (all
species combined)
N = 54,445
Incidence (%)
17.4
16.1
9.7
12.6
11.3
5.5
4.2
33.0
Jones ME, et al. Ann Clin Microbiol Antmicrob 2004;3
ICU Bloodstream Infections
Organism Distribution (1989-1998, NNIS)
70 ICUs, n = 50,091
Coagulase negative staph
Staphylococcus aureus
Enterococcus spp
Enterobacteriaceae
Candida albicans
Pseudomonas aeruginosa
39.3%
10.7%
10.3%
10.0%
4.9%
3.0%
Fridkin and Gaynes, Clin Chest Med, 20:303, 1999
Hospital-acquired pneumonia Pathogens
causing infection, USA vs Canada
Organism
USA (%)
Canada (%)
S. aureus
23.0
22.5
P. aeruginosa
18.2
17.6
H. influenzae
10.1
11.0
Klebsiella spp.
8.7
8.7
S. pneumoniae
7.6
8.1
Enterobacter sp
7.8
6.1
E. coli
4.4
5.7
S. maltophilia
3.5
3.7
S. marcescens
2.6
2.4
Jones RN. Chest 2001;119
TGH ICU: Total Respiratory Tract
Positive Cultures = 280
Potential Amp C carriers: Enterobacter clocae, Serratia marcescens, Citrobacter freundii,
Enterobacter aerogenes, Enterobacter species, Proteus mirabilis, Citrobacter koseri,
Acinetobacter, Proteus vulgaris
Courtesy of Beth Allan, TGH Pharmacy
When to Suspect P. aeruginosa
Retrospective analysis from 4 hospitals
151 patients and 152 controls
– P. aeruginosa caused 6.8% of 4,114 episodes of
Gram-negative bacteremia
– Risk factors: severe immunodeficiency, age >90,
antimicrobials within 30 days, presence of central
venous catheter or a urinary device
If ≥2 had over 25% risk for P. aeruginosa
V Schechner et al, CID 48:580-6, 2009
Risk factors for P. aeruginosa in
pneumonia
– Structural lung disease (bronchiectasis)
– Corticosteroids (> 10 mg prednisone/day)
– Broad-spectrum antibiotics for > 7 days within
the past month
– Malnutrition
– Late-onset HAP (>5 days)
AMJRCCM 1999:160, Semin Resp Infect 13:1998; Infect Dis Clin North Amer 12:1998
Antimicrobial Resistance in P. aeruginosa
Antimicrobial Resistance in P. aeruginosa
Intrinsic resistance to most antibiotics is
attributed to:
– Efflux pumps: Chromosomally-encoded genes (e.g.
mexAB-oprM, mexXY, etc) and
– Low permeability of the bacterial cellular envelope
Acquired resistance with development of multidrug resistant strains by:
– Mutations in chromosomally-encoded genes, or
– Horizontal gene transfer of antibiotic resistance
determinants
Antimicrobial Resistance in the USA
Rehm SJ et al. CID 2006;42(Suppl 2)
Susceptibility of Canadian Isolates of
Pseudomonas aeruginosa
100
N = 6783; Blood = 3840 (57%); Resp = 1659 (24%)
90
80
% Susceptible
70
Cipro
Tobra
Pip/Tazo
Imipenem
60
50
40
30
20
10
0
1997
1998
1999
2000-2002*
Year
SENTRY. CID 2001:32; *Jones ME. Ann Clin Microbiol Antimicrob 2004;3
P. aeruginosa – ciprofloxacin resistance, 2004-7
Percent resistant to ciprofloxacin
MSH
one isolate per patient per visit; admit=in hosp<3 days
2004
2005
2006
2007
70
60
50
40
30
20
10
0
Perinatal
OPD
ER
Inpt-admit Inpt-noso ICU-admit ICU-noso
P. aeruginosa – gentamicin resistance, 2004-7
Percent resistant to ciprofloxacin
MSH
one isolate per patient per visit; admit=in hosp<3 days
50
45
40
35
30
25
20
15
10
5
0
2004
2005
2006
2007
Perinatal
OPD
ER
Inpt-admit Inpt-noso ICU-admit ICU-noso
P. aeruginosa – tobramycin resistance, 2004-7
Percent resistant to ciprofloxacin
MSH
one isolate per patient per visit; admit=in hosp<3 days
2004
2005
2006
2007
30
25
20
15
10
5
0
Perinatal
OPD
ER
Inpt-admit Inpt-noso ICU-admit ICU-noso
P. aeruginosa – ceftazidime resistance, 2004-7
Percent resistant to ciprofloxacin
MSH
one isolate per patient per visit; admit=in hosp<3 days
50
45
40
35
30
25
20
15
10
5
0
2004
2005
2006
2007
Perinatal
OPD
ER
Inpt-admit Inpt-noso ICU-admit ICU-noso
P. aeruginosa – Pip-tazo resistance, 20047 MSH
Percent resistant to ciprofloxacin
one isolate per patient per visit; admit=in hosp<3 days
2004
2005
2006
2007
40
35
30
25
20
15
10
5
0
Perinatal
OPD
ER
Inpt-admit Inpt-noso ICU-admit ICU-noso
P. aeruginosa – Meropenem resistance,
2004-7 MSH
Percent resistant to ciprofloxacin
one isolate per patient per visit; admit=in hosp<3 days
50
45
40
35
30
25
20
15
10
5
0
2004
2005
2006
2007
Perinatal
OPD
ER
Inpt-admit Inpt-noso ICU-admit ICU-noso
Antimicrobial Therapy of P. aeruginosa
Likelihood of Inadequate Therapy
Inadequate therapy more likely if antibiotic resistance is present,
and certain organisms (antibiotic resistant ones) more
commonly associated with inadequate therapy.
40
35
30
25
%
Inadequate
Rx
20
15
10
Other = H. infl, E. coli, P. mirabilis, S.
marcescens
5
0
PA
SA Acin Other KE
Kollef CID 2000; 31: S 131-138
Case #1
MQ 42 y/o mailman; stubbed left toe
Walk in clinic
Keflex
5 days later
fatigue, tired, no
improvement
d/c keflex, start
Cloxacillin
3 days later
fever, fatigue,
increased redness in toe
What therapy would you choose?
Case Study Continued
Assessed in E.R. - WBC = 32x109 with
blasts
Transferred on I.V. Cloxacillin
4 days later
-
Fever and Rash
-
Diagnosis?
Legs
Left Arm
Case Study... continued
Bone Marrow

AML
Blood cultures drawn on admission grew
gram negative bacilli at 24 hours
At 48 hours culture was positive for ……?
Case #2
73 y/o male, relapsed ALL:
– Fatigue, WBC = 19x109/L (1%
blasts)
– Reinduction chemotherapy
– Day 14 - home on Septra; WBC =
0.5
Case #2
Day 15 - 38.2oC; pain at Hickman site
Returned to ER
Swab - no bacteria/pus
Admit to ward
What therapy would you choose?
Case Study
Admitted and started on Vancomycin
6 hours post-admission - hypotensive;
tachycardia; 39.6oC
Remove Hickman line; continue
vancomycin; transfer to ICU
4 hours later - black, necrotic lesion at
Hickman site with spreading erythema
4 hours later - died
10 hours post-admission:
Case Study
Blood cultures:
- 24 hours post-admission:
Gram negative bacilli
- 48 hours culture was positive for ….?
TGH ICU Isolates 2007 Antibiogram
(% Susceptible)
Species (N)
Pip/Tazo
Imipenem
Ceftazidime
Ciprofloxacin
Tobramycin
P. aeruginosa (71)
83
65
63
63
76
Kleb. species (31)
87
100
97
97
100
E. coli (27)
96
100
81
56
78
E. cloacae (18)
78
100
78
94
100
S. marcescens (13)
92
100
92
85
92
-
-
-
-
-
C. freundii (6)
83
100
50
83
100
E. aerogenes (4)
100
100
100
100
100
Enterobacter sp. (3)
100
100
67
100
100
S. maltophilia (8)
Empiric Coverage of Gram Negative
Organisms with Selected Agents
1: Consider Amp Cs not induced
*MDR pathogens: Pseudomonas aeruginosa, Stenotrophomonas maltophilia
Courtesy of Beth Allan, TGH Pharmacy
ICU-Specific Antibiogram
Imipenem + amikacin
+ vancomycin
Ceftazidime + amikacin
+ vancomycin
Piperacillin/tazobactam
+ amikacin + vancomycin
Aztreonam + amikacin
+ vancomycin
0
20
40
60
80
100
% Susceptibility
Trouillet JL, et al. Am J Respir Crit Care Med. 1998;157:531
Combination Therapy Against
Pseudomonas aeruginosa
Due to increasing resistance patterns,
combination therapy may be required for
empirical treatment
Fluoroquinolone treatment plus a cephalosporin
achieves in vitro synergy in 60-80% of the
P.
aeruginosa strains tested.
– 92% synergistic when strains were resistant to one or
both agents
– Prevented resistance development
61% synergistic effect of meropenem and
ciprofloxacin at 1x MIC against P. aeruginosa.
Ermertcan et al. Scand J Infect Dis. 2001;33(11):818-21
Fish et al. J Antimicrob Chemother. 2002 Dec;50(6):1045-9

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