Pseudomonas: Microbiologic and Clinical Features

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Pseudomonas Microbiologic and Clinical Features
T. Mazzulli, MD, FRCPC, FACP Microbiologist and
Infectious Diseases Consultant Mount Sinai
Hospital/UHN

2
Objectives

• Review the current epidemiology of antimicrobial
  resistance of key bacterial pathogens
• Discuss the mechanism of resistance,
  cross-resistance and co-resistance and laboratory
  detection
• Review recommendations for treatment and control
  of multi-drug resistant pathogens

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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

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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

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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

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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

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P. aeruginosa on blood agar
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MacConkey Agar
Non-Lactose Fermenter
Lactose Fermenter
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MacConkey Agar
P. aeruginosa
Mucoid P. aeruginosa
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Epidemiology and Clinical Aspects of P. aeruginosa
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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

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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

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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
• Swimmers 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

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Hospital-acquired gram negative organisms
Distribution in the ICU, 2004-2007
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Bacterial Infections in the ICUOrganism
Distribution in North America
SENTRY 2001 24-36 medical centers in N.A., n
1321

• Staphylococcus aureus 24.1
• Pseudomonas aeruginosa 12.2
• Escherichia coli 10.1
• Klebsiella species 8.9
• Enterococcus species 7.2
• Coagulase negative staph 7.0
• Enterobacter species 7.0
• Acinetobacter species 4.0
• Serratia species 3.0
• Stenotrphomonas maltophilia 3.0

Jones, Sem Resp Crit Care Med, 2003
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Incidence of Pathogens from ICUs in Canada (87
hospitals sites) 2000 to 2002
Organism Incidence ()
S. aureus 17.4
Coag. Neg Staphylococcus 16.1
Enterococcus spp. 9.7
E. coli 12.6
P. aeruginosa 11.3
K. pneumoniae 5.5
Enterobacter cloacae 4.2
Enterobacteriaceae (all species combined) 33.0
N 54,445
Jones ME, et al. Ann Clin Microbiol Antmicrob
20043
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ICU Bloodstream InfectionsOrganism Distribution
(1989-1998, NNIS)
70 ICUs, n 50,091

• Coagulase negative staph 39.3
• Staphylococcus aureus 10.7
• Enterococcus spp 10.3
• Enterobacteriaceae 10.0
• Candida albicans 4.9
• Pseudomonas aeruginosa 3.0

Fridkin and Gaynes, Clin Chest Med, 20303, 1999
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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 2001119
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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
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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 gt90,
  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 48580-6, 2009
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Risk factors for P. aeruginosa in pneumonia

• Structural lung disease (bronchiectasis)
• Corticosteroids (gt 10 mg prednisone/day)
• Broad-spectrum antibiotics for gt 7 days within
  the past month
• Malnutrition
• Late-onset HAP (gt5 days)

AMJRCCM 1999160, Semin Resp Infect 131998
Infect Dis Clin North Amer 121998
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Antimicrobial Resistance in P. aeruginosa
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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
  multi-drug resistant strains by
• Mutations in chromosomally-encoded genes, or
• Horizontal gene transfer of antibiotic resistance
  determinants

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Antimicrobial Resistance in the USA
Rehm SJ et al. CID 200642(Suppl 2)
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Susceptibility of Canadian Isolates of
Pseudomonas aeruginosa
N 6783 Blood 3840 (57) Resp 1659 (24)
Susceptible
1997 1998 1999 2000-2002
Year
SENTRY. CID 200132 Jones ME. Ann Clin
Microbiol Antimicrob 20043
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P. aeruginosa ciprofloxacin resistance, 2004-7
MSHone isolate per patient per visit admitin
hosplt3 days
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P. aeruginosa gentamicin resistance,
2004-7MSHone isolate per patient per visit
admitin hosplt3 days
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P. aeruginosa tobramycin resistance,
2004-7MSHone isolate per patient per visit
admitin hosplt3 days
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P. aeruginosa ceftazidime resistance,
2004-7MSHone isolate per patient per visit
admitin hosplt3 days
30
P. aeruginosa Pip-tazo resistance, 2004-7
MSHone isolate per patient per visit admitin
hosplt3 days
31
P. aeruginosa Meropenem resistance, 2004-7
MSHone isolate per patient per visit admitin
hosplt3 days
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Antimicrobial Therapy of P. aeruginosa
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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.

Other H. infl, E. coli, P. mirabilis, S.
marcescens
SA
Other
Kollef CID 2000 31 S 131-138
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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

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(No Transcript)
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What therapy would you choose?
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Case Study Continued

• Assessed in E.R. - WBC 32x109 with blasts
• Transferred on I.V. Cloxacillin
• 4 days later - Fever and Rash
• - Diagnosis?

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Legs Left Arm
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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 ?

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Case 2

• 73 y/o male, relapsed ALL
• Fatigue, WBC 19x109/L (1 blasts)
• Reinduction chemotherapy
• Day 14 - home on Septra WBC 0.5

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Case 2

• Day 15 - 38.2oC pain at Hickman site
• Returned to ER
• Swab - no bacteria/pus
• Admit to ward

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What therapy would you choose?
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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

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10 hours post-admission
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Case Study

• Blood cultures
• - 24 hours post-admission
• Gram negative bacilli
• - 48 hours culture was positive for .?

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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
S. maltophilia (8) - - - - -
C. freundii (6) 83 100 50 83 100
E. aerogenes (4) 100 100 100 100 100
Enterobacter sp. (3) 100 100 67 100 100
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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
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ICU-Specific Antibiogram
Imipenem amikacin vancomycin
Ceftazidime amikacin vancomycin
Piperacillin/tazobactam amikacin vancomycin
Aztreonam amikacin vancomycin
Trouillet JL, et al. Am J Respir Crit Care Med.
1998157531
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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.
200133(11)818-21 Fish et al. J Antimicrob
Chemother. 2002 Dec50(6)1045-9