CASE 1
A 25 year old male is brought to the emergency room by his wife with a 2 week
history of easy fatigability, dyspnea on exertion, easy bruising and bleeding gums. Over
the last 24 hours, the patient noted a fever of 104° F orally, shaking chills, mental
confusion and severe weakness so that the patient could not get out of bed. The patient
denies cough, sputum production, nausea, vomiting, stiff neck, dysuria, frequency of
urination. PM Hx: non-contributory
Physical Examination: Toxic appearing, pale patient. VS: HR 120 weak, BP 85 palpable, R22, T 39.7° orally.
Mouth: bleeding gums. Nodes: enlarged non-tender cervical and axillary nodes. Neck: supple, full range of motion.
Lungs: Clear to A&P. CV - S1. and S2 NL no S3/ S4, SEM 3/6 at LLSB. Abd: soft non-tender, liver span 14 cm and tender, spleen tip felt.
Ext: cool, purplish discoloration. Skin: Scattered petechiae, black raised 1 cm lesion on (L) leg, no fluctuance
or drainage of the lesion. Rectal: No external lesions, digital exam not done.
Neuro: sleepy, arousable, oriented to person not time or place, cranial nerves
2-12 intact, reflexes 2+ symmetrical, Babinsky downgoing
Laboratory: CBC - Hgb 7.0 am, WBC 1,000/mm3, 20 seg, 20 blasts 45 L, 15 M, Plt. 7000/mm3. CXR - wnl. UA wnl. Urine C&S sent blood C&S x 2 sent.
Course: The patient was started on piperacillin and gentamicin, and given IV fluids to maintain his systolic blood pressure at 100. Concomitantly, the patient was given irradiated blood products, 4 units of packed red blood cells and 12 units of platelets. A bone marrow was done. The diagnosis of acute lymphocytic leukemia was made. The next day blood cultures were growing a gram negative rod which was non-lactose fermenting. The organism was later identified as Pseudomonas aeruginosa.
QUESTIONS:
1. Create a problem list from the history.
2. Identify and explain the significance of each pertinent physical finding.
3. Review the lab data and explain the findings.
4. What is diagnosis based on History, physical and lab data. Describe succinctly, the disease this case represents
5. Describe the offending organism, its morphological, cultural characteristics and their normal habitat.
6. What are the possible sources of infection? What is the most likely source of infection in this patient?
The source of infection is the gastrointestinal tract and environment.
7. How do these organisms gain access to humans? What are the risk factors for Pseudomonas infection? What are the risk factors for infection in this patient?
Neutropenia is the major risk factor in this patient.
8. How do they invade and spread in humans? What virulence factors are associated with the pathogenesis of Pseudomonas sepsis?
Invasive and Toxinogenic
9. What defenses humans have against these organisms?
10. How do these organisms able to overcome human defenses?
11. What is the end result of this battle between organisms and humans?
Necrotizing infection
12. Why is this patient hypotensive? What is the pathogenesis of septic shock?
The patient is septic. Criteria for sepsis are:
The lipopolysaccharide (LPS) in gram negative organism triggers complement, clotting, fibrinolytic and kinin pathways.
Fever and inflammation are mediated by cytokines that are released in response to LPS.
Cytokines which are released include TNF-" , interleukin-1 (IL-1) interferon-m ).
Interleukin-1 is the endogenous pyrogen. TNF-" is the most potent mediator of the pathophysiology of the gram negative sepsis syndrome.
13. How do you diagnose this infection?
Gram stain and culture of appropriate secretions/blood.
14. What is the pathogenesis of ecthyma gangrenosum?
Is the result of direct invasion and destruction of the blood vessel walls by the organism.
15. What will be your therapeutic strategy? Why was the patient started on piperacillin and gentamicin? What other antibiotics could be used to treat Pseudomonas bacteremia?
16. What factors are associated with a poor outcome in patients with Pseudomonas sepsis?
17. How can you prevent it from spreading to others? Prevent its occurrence?
18. What are other clinical infections with these organisms?
19. Is there a drug which directly inhibits the pathogenesis of sepsis and how?
Drotrecoigin alfa (activated). Trade name is Xigris. It is biologically engineered recombinant form of a nartural blood product which is human activated protein C. It interferes with blood clotting which prevents DIC by destroying activated factorVa and VIIIa. It also decreases inflammation. It is approved by the FDA for use in patients with severe sepsis who are at high risk of death. Its major side effect is a 3.5% incidence of bleeding. It is administered intravenously and costs about $7,000 per treatment.