Pseudomonas: Microbiologic and Clinical Features
T. Mazzulli, MD, FRCPC, FACP
Microbiologist and Infectious DiseasesConsultant
Mount Sinai Hospital/UHN
Objectives
Review the current epidemiology of antimicrobial resistance of key bacterial pathogensDiscuss the mechanism of resistance, cross-resistance and co-resistance 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
MacConkey Agar
Non-Lactose Fermenter
Lactose Fermenter
MacConkey Agar
P. aeruginosa Mucoid P. aeruginosa
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 humansNormal 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
Hospital-acquired gram negative organisms Distribution in the ICU, 2004-2007
0102030405060708090
100
2005 2006 2007
Num
ber o
f iso
late
s (o
ne p
er p
atie
nt)
OtherSerratiaAcinetobacterStenotrophomonasEnterobacter/citrobacterE. coliKlebsiella spp.P. aeruginosa
Bacterial Infections in the ICU:Organism Distribution in North America
Staphylococcus aureus 24.1Pseudomonas aeruginosa 12.2Escherichia coli 10.1Klebsiella species 8.9Enterococcus species 7.2Coagulase negative staph 7.0Enterobacter species 7.0Acinetobacter species 4.0Serratia species 3.0Stenotrphomonas maltophilia 3.0
SENTRY: 200124-36 medical centers in N.A., n = 1321
Jones, Sem Resp Crit Care Med, 2003
Incidence of Pathogens from ICUs in Canada Incidence of Pathogens from ICUs in Canada (87 hospitals sites): 2000 to 2002(87 hospitals sites): 2000 to 2002
OrganismOrganism Incidence (%)Incidence (%)
S. aureusS. aureus 17.417.4
Coag. Neg StaphylococcusCoag. Neg Staphylococcus 16.116.1
Enterococcus spp.Enterococcus spp. 9.79.7
E. coliE. coli 12.612.6
P. aeruginosaP. aeruginosa 11.311.3
K. pneumoniaeK. pneumoniae 5.55.5
Enterobacter cloacaeEnterobacter cloacae 4.24.2
Enterobacteriaceae (all Enterobacteriaceae (all species combined)species combined)
33.033.0
Jones ME, et al. Ann Clin Microbiol Antmicrob 2004;3N = 54,445
ICU Bloodstream InfectionsOrganism Distribution (1989-1998, NNIS)
Coagulase negative staph 39.3%Staphylococcus aureus 10.7%Enterococcus spp 10.3%Enterobacteriaceae 10.0%Candida albicans 4.9%Pseudomonas aeruginosa 3.0%
70 ICUs, n = 50,091
Fridkin and Gaynes, Clin Chest Med, 20:303, 1999
Hospital-acquired pneumonia Pathogens Hospital-acquired pneumonia Pathogens causing infection, USA vs Canadacausing infection, USA vs Canada
OrganismOrganism USA (%)USA (%) Canada (%)Canada (%)
S. aureusS. aureus 23.023.0 22.522.5
P. aeruginosaP. aeruginosa 18.218.2 17.617.6
H. influenzaeH. influenzae 10.110.1 11.011.0
Klebsiella spp.Klebsiella spp. 8.78.7 8.78.7
S. pneumoniaeS. pneumoniae 7.67.6 8.18.1
Enterobacter spEnterobacter sp 7.87.8 6.16.1
E. coliE. coli 4.44.4 5.75.7
S. maltophiliaS. maltophilia 3.53.5 3.73.7
S. marcescensS. marcescens 2.62.6 2.42.4
Jones RN. Chest 2001;119
Potential Amp C carriers: Enterobacter clocae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, Enterobacter species, Proteus mirabilis, Citrobacter koseri, Acinetobacter, Proteus vulgaris
TGH ICU: Total Respiratory Tract Positive Cultures = 280
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 multi-drug resistant strains by:– Mutations in chromosomally-encoded genes, or – Horizontal gene transfer of antibiotic resistance
determinants
Rehm SJ et al. CID 2006;42(Suppl 2)
Antimicrobial Resistance in the USA
Susceptibility of Canadian Isolates of Pseudomonas aeruginosa
0
10
20
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60
70
80
90
100
Cipro
Tobra
Pip/Tazo
Imipenem
% S
usc
epti
ble
Year
SENTRY. CID 2001:32; *Jones ME. Ann Clin Microbiol Antimicrob 2004;3
1997 1998 1999 2000-2002*
N = 6783; Blood = 3840 (57%); Resp = 1659 (24%)
P. aeruginosa – ciprofloxacin resistance, 2004-7 MSH
one isolate per patient per visit; admit=in hosp<3 days
0
10
20
30
40
50
60
70
Perc
ent r
esis
tant
to c
ipro
floxa
cin
Perinatal OPD ER Inpt-admit Inpt-noso ICU-admit ICU-noso
2004
2005
2006
2007
P. aeruginosa – gentamicin resistance, 2004-7MSH
one isolate per patient per visit; admit=in hosp<3 days
05
101520253035404550
Perc
ent r
esis
tant
to c
ipro
floxa
cin
Perinatal OPD ER Inpt-admit Inpt-noso ICU-admit ICU-noso
2004
2005
2006
2007
P. aeruginosa – tobramycin resistance, 2004-7MSH
one isolate per patient per visit; admit=in hosp<3 days
0
5
10
15
20
25
30
Perc
ent r
esis
tant
to c
ipro
floxa
cin
Perinatal OPD ER Inpt-admit Inpt-noso ICU-admit ICU-noso
2004
2005
2006
2007
P. aeruginosa – ceftazidime resistance, 2004-7MSH
one isolate per patient per visit; admit=in hosp<3 days
05
101520253035404550
Perc
ent r
esis
tant
to c
ipro
floxa
cin
Perinatal OPD ER Inpt-admit Inpt-noso ICU-admit ICU-noso
2004
2005
2006
2007
P. aeruginosa – Pip-tazo resistance, 2004-7 MSH
one isolate per patient per visit; admit=in hosp<3 days
0
5
10
15
20
25
30
35
40
Perc
ent r
esis
tant
to c
ipro
floxa
cin
Perinatal OPD ER Inpt-admit Inpt-noso ICU-admit ICU-noso
2004
2005
2006
2007
P. aeruginosa – Meropenem resistance, 2004-7 MSH
one isolate per patient per visit; admit=in hosp<3 days
05
101520253035404550
Perc
ent r
esis
tant
to c
ipro
floxa
cin
Perinatal OPD ER Inpt-admit Inpt-noso ICU-admit ICU-noso
2004
2005
2006
2007
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.
0
5
10
15
20
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35
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PA Acin KE
% InadequateRx
Kollef CID 2000; 31: S 131-138SA Other
Other = H. infl, E. coli, P. mirabilis, S. marcescens
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
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
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
Trouillet JL, et al. Am J Respir Crit Care Med. 1998;157:531
0 20 40 60 80 100
% Susceptibility
Imipenem + amikacinImipenem + amikacin+ vancomycin+ vancomycin
Ceftazidime + amikacinCeftazidime + amikacin+ vancomycin+ vancomycin
Piperacillin/tazobactamPiperacillin/tazobactam + amikacin + vancomycin+ amikacin + vancomycin
Aztreonam + amikacinAztreonam + amikacin+ vancomycin+ vancomycin
Combination Therapy Against Pseudomonas aeruginosa
Due to increasing resistance patterns, combination therapy may be required for empirical treatmentFluoroquinolone 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