Pseudomonas: Microbiologic and Clinical Features

1. Pseudomonas: Microbiologic and Clinical Features

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

3. 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

4. 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

5. 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

6. 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

7. P. aeruginosa on blood agar

8. MacConkey Agar

9. MacConkey Agar

10. Epidemiology and Clinical Aspects of P. aeruginosa

11. 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

12. 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

13. 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

14. Hospital-acquired gram negative organisms Distribution in the ICU, 2004-2007

15. Bacterial Infections in the ICU:Organism Distribution in North America 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

16. Incidence of Pathogens from ICUs in Canada (87 hospitals sites): 2000 to 2002

17. 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%

18. Hospital-acquired pneumonia Pathogens causing infection, USA vs Canada

20. 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

21. 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)

22. Antimicrobial Resistance in P. aeruginosa

23. 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

25. Susceptibility of Canadian Isolates of Pseudomonas aeruginosa

26. P. aeruginosa � ciprofloxacin resistance, 2004-7 MSHone isolate per patient per visit; admit=in hosp<3 days

27. P. aeruginosa � gentamicin resistance, 2004-7MSHone isolate per patient per visit; admit=in hosp<3 days

28. P. aeruginosa � tobramycin resistance, 2004-7MSHone isolate per patient per visit; admit=in hosp<3 days

29. P. aeruginosa � ceftazidime resistance, 2004-7MSHone isolate per patient per visit; admit=in hosp<3 days

30. P. aeruginosa � Pip-tazo resistance, 2004-7 MSHone isolate per patient per visit; admit=in hosp<3 days

31. P. aeruginosa � Meropenem resistance, 2004-7 MSHone isolate per patient per visit; admit=in hosp<3 days

32. Antimicrobial Therapy of P. aeruginosa

33. 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.

34. 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

36. What therapy would you choose?

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

39. 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 ��?

40. Case #2 73 y/o male, relapsed ALL: Fatigue, WBC = 19x109/L (1% blasts) Reinduction chemotherapy Day 14 - home on Septra; WBC = 0.5

42. What therapy would you choose?

43. 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

45. Case Study Blood cultures: - 24 hours post-admission: Gram negative bacilli - 48 hours culture was positive for �.?

46. TGH ICU Isolates 2007 Antibiogram (% Susceptible)

48. ICU-Specific Antibiogram

49. 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.