1 / 74

FEBRILE NEUTROPENIA

Saima Abbas M.D Infectious Diseases Fellow-PGY5. FEBRILE NEUTROPENIA. Why is this an Oncologic emergency ??. Infection + ABX + Immune system = cure. Normal Gross Anatomy Skin Integrity Intact mucous membranes Intact ciliary function Absence of Foreign Bodies. Innate Immunity

Thomas
Download Presentation

FEBRILE NEUTROPENIA

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Saima Abbas M.D Infectious Diseases Fellow-PGY5 FEBRILE NEUTROPENIA

  2. Why is this an Oncologic emergency ??

  3. Infection + ABX + Immune system = cure • Normal Gross Anatomy • Skin Integrity • Intact mucous membranes • Intact ciliary function • Absence of Foreign Bodies • Innate Immunity ( PMN, Macrophages, NK cells, Mast cells and basophils) • Complement • Adaptive immunity T cells CD 4 and CD 8 B cells

  4. Case 1July 10th 2009 - NF 1 You are paged at 5:00am by the nurse taking care of Mr. Thomas on 4 AB He spiked a fever of 38 C (100.4F) one hour ago. -There is no order for Tylenol.

  5. ~ You check your Hem Oncology List . Per sign out: The patient was recently diagnosed with AML is S/P chemotherapy and is stable. • You can • Order Tylenol and take the next page. • OR…..

  6. OR Am I missing febrile Neutropenia??? • If you are alert, you think…

  7. What are the facts you need to know? • Does 38  C define febrile neutropenia? • What’s his Absolute Neutrophil Count? • Any transfusion in the last 6 hours?

  8. Definition of Fever in FN • A single oral temp  38.3  C (101  F) or • A temperature of  38  C (100.4F) on two occasions separated by 1 hour

  9. You request her to repeat the temperature and she reports 38. 2 C (100.8 F)

  10. Don’t be tricked • If temperature 37  38 C , repeat temperature in 1 hour to see if the above criteria for treatment are met • Clinical signs of septicemia • Good history of fever detected by patient before admission and afebrile when you evaluate the patient.

  11. Definition of Neutropenia • ANC  500/mm3 or • 1000/mm3 and predicted decline to  500/mm ~ Clin Inf Dis, 2002;34:730-51

  12. ANC : Mr. Thomas • WBC 0.7 • Segs = 38% • Bands = 2%

  13. Absolute Neutrophil Count (Total # of WBC) x (% of Neutrophils) = ANC • Take the percent of neutrophils (may also be polys or segs) + percent bands • Convert percent to a decimal by dividing by 100 (Example 40% = 40/100 = 0.40) (*move the decimal 2 points to the left) • Multiply this number by the total White Blood Cells (WBC)

  14. Calculation 0.7 X 1000 = 70040% =40/100=0.40 700 X 0.40 = 280

  15. Neutropenia • Normal ANC 1500 to 8000 cells/mm³ • Neutropenia: ANC < 1500 cells / mm3 • Mild Neutropenia: 1000-1500 cells / mm3 • Moderate Neutropenia: 500-999 cells / mm3 • Severe Neutropenia: < 500 cells / mm3 • Profound Neutropenia: <100 cells/ mm³

  16. When Does Neutropenia Occur? • Most chemotherapy agents/protocols cause neutropenia nadir at 10-14 days • But can see anytime from a few days after chemotherapy to up to 4-6 weeks later depending on the agents used

  17. Risk of Infection as Absolute Neutrophil Count Declines

  18. Epidemiology • Up to 60% febrile neutropenia episodes = infection (microbiological or clinical) • ~20% patients with ANC <100 cells/mm³ with febrile neutropenia episodes have bacteremias.

  19. Epidemiology --NEJM, 1971;284:1061 Retrospective data have shown that • ~ 50 % of Pseudomonas Aeruginosa Bacteremia result in death within 72 hours when ANC is < 1000 • Early trials aimed at Pseudomonas showed thatCarbapenicillin /Gentamicin decreased Mortality by 33 % ~Journal of Infectious diseases, 1978;147:14

  20. Epidemiology Viscoli et al, Clin Inf Dis;40:S240-5 • Changing etiology of bacteremia IATG-EORTC 1973-2000 trials of febrile neutropenia • Gram positive dominant since mid 1980s • 1) More intensive chemoTx • Mucositis • 2) In-dwelling catheters • Cutaneous-IV portal • 3) Selective antiBx pressure • Fluoroquinolones • Co-trimoxazole • 4) Antacids • Promote oro-oesophageal colonisation with GPC Gram negative resurgence

  21. Duration of Neutropenia • < 7 days LOW risk • 7 to 14 days INTERMEDIATE RISK • > 14 days HIGH RISK

  22. Duration Of Neutropenia 1988,Rubin and colleagues • < 7 days of neutropenia ~ response rates to initial antimicrobial therapy was 95%, compared to only 32% in patients with more than 14 days of neutropenia ( <.001) ~ patients with intermediate durations of neutropenia between 7 and 14 days had response rates of 79%

  23. Common Microbes Gram-positive cocci and bacilli • Staph. aureus • Staphylococcus epidermidis • Enterococcus faecalis/faecium • Corynebacterium species Gram-negative • bacilli and cocci • Escherichia coli • Klebsiella species • Pseudomonas aeruginosa FUNGI • Candida- Non albicans emerging • Aspergillus >> in HSCT

  24. Initial evaluation Ensure Hemodynamic Stability and No NEW ORGAN DYSFUNCTION • History • Underlying disease, remission and transplant status- spleen +/- • Chemotherapy • Drug history (steroids, any previous antibiotics) • Allergies • Focused Review of systems • Transfusions • Can cause fevers • Lines or in-dwelling hardware

  25. THINK Strep. Pneumoniae Neisseriameningitidis HemophilusInfluenzae • Splenectomy

  26. Exam (be prepared to find no signs of inflammation) • HEENT Look in the mouth any oral sores – periodontium, the pharynx • Lungs • Abdomen for tenderness- RLQ (signs of Typhilitis) • Perineum including the anus -No rectal exam !

  27. Skin Exam- Ask the patient for any area of tenderness? Skin – • Bone marrow aspirations sites, • vascular catheter access sites • and tissue around the nails • Rashes (Drug eruptions/herpes zoster reactivation / Petechial rashes all are common in these patients)

  28. Febrile neutropeniaInvestigation • Complete Blood Count (with Differential) -White cells, haemoglobin, platelets • Biochemistry -Electrolytes, urea, creatinine, Liver function • Microbiology -Blood cultures (peripheral and all central line lumens) -Oral ulcers or sores –send swabs ( Viral Cx and fungal Cx ) -Exit site swabs -Wound swabs -Urine Cultures (SSx/Foley Catheter) [- pyuria ?? UA] -Stool Cultures and CDiff Toxin/PCR • Radiology -Chest Xray +/- CT abdomen/pelvis

  29. Lumbar puncture- • Examination of CSF specimens is not recommended as a routine procedure but should be considered if a CNS infection is suspected and thrombocytopenia is absent or manageable.

  30. Skin lesions • Aspiration or biopsy of skin lesions suspected of being infected should be • performed for cytologic testing, Gram staining, and culture

  31. IMAGING in FN • CXR if Symptomatic or if out pt Rx considered • High resolution CT Chest Indicated ONLY if persistent fevers with pulmonary symptoms after initiation of empiric Abx • CTA if suspect PE • CT abdomen for Necrotizing Enterocolitis or Typhilitis • CT brain R/o ICH / MRI of the spine or brain - more for evaluation of metastatic disease than FN

  32. Stratify risk of complications 1. Neutropenia •  with severity of neutropenia (< 50/mm3) •  with duration of neutropenia (>7 days) 2.Bacteremia • Gram negative > gram positive 3.Underlying malignancy and status • Acute Leukemia • Relapsed disease • Solid malignancies: Local effects eg obstruction, invasion 4.Co-morbidities, age >60

  33. HIGH risk Patients • • Prolonged Neutropenia (>14 days) • Haematological malignancy/ Allogenic HSCT • • Myelosuppresive chemotherapy • • Concurrent chemotherapy and radiotherapy • • Age >60 • • Co-morbidities eg. Diabetes, poor nutritional status. • • Bone marrow involvement of cancer • • Delayed surgical healing or open wounds • • Significant mucositis • • Unstable (eg hypotensive, oliguric) • • On steroid dose >20mg prednisone daily • • Recent hospitalization for infection

  34. a Concomitant condition of significance (e.g.,shock, hypoxia, pneumonia, or other deep organ infection, vomiting, or diarrhea).

  35. Risk model • Model 2 • (Klatersky et al MASCC 2000 J Clin Onc) • No or Mild symptoms 5 • Moderate symptoms 3 • No Hypotension 5 • No COPD 4 • Solid tumour / 4 • Haem malignancy • (no fungal infection) • Outpatient 3 • No dehydration 3 • Age <60 yrs 2 • LOW RISK=score>20

  36. ORAL vs IV • For patients who are low risk for developing infection-related complications during the course of neutropenia, ~ Oral ciprofloxacin plus amoxicillin/clavulanate ~ Oral ciprofloxacin plus clindamycin for PCN allergy

  37. If inpatient and high risk • EMPIRIC ANTIMICROBIAL THERAPY after Blood Cultures.Must be initiated within 1 hour

  38. THREE approaches for IV EMPIRIC therapy • IV MONO THERAPY • IV DUAL THERAPY • COMBINATION THERAPY Mono or dual therapy + VANCOMYCIN

  39. Monotherapy IV • Extended spectrum Antipseudomonal Cephalosporins • Cefepime • Ceftazidime • Carbapenem • Imipenem –Cilastatin • Meropenem • Anti –Pseudomonal PCN • Piperacillin- Tazobactam • Ticarcillin- Clavulanic acid

  40. DUAL therapy 1. an aminoglycoside plus an antipseudomonal penicillin (with or without a beta-lactamase inhibitor) or an extended-spectrum antipseudomonal cephalosporin,

  41. Dual therapy (2) ciprofloxacin plus an antipseudomonal penicillin. • Indications • Unstable patient • H/O P. aeruginosa colonization or Invasive disease

  42. 5 Indications for Vancomycin 1. clinically suspected serious catheter-related infections 2. known colonization with penicillin- and cephalosporin-resistant pneumococci or MRSA, 3. positive results of blood culture for gram-positive • hypotension or other evidence of cardiovascular impairment 5. H/O ciprofloxacin or trimethoprim-sulfamethoxazole

  43. vancomycin resistant enterococcus • Linezolid • Daptomycin (avoid for pneumonia) • Quinopristin- Dalfopristin

  44. PCN allergy • NON – ANAPHYLACTIC If not allergic to cephalosporins ~ Cefepime • ANAPHYLACTIC and allergic to cephalosporins- ~Aztreonam +/- Aminoglycoside or a FQ +/- Vancomycin if indicated

  45. MAINTAIN BROAD SPECTRUM ACTIVITY FOR A MINIMUM OF 7 DAYS OR UNTIL ANC >500

  46. Antibiotic stopping guideIDSA, Clin Infect Disease, 2002 • Minimum 1 week of therapy if • Afebrile by day 3 • Neutrophils >500/mm3 (2 consecutive days) • Cultures negative • Low risk patient, uncomplicated course • > 1 week of therapy based if • Temps slow to settle (>3 days) • Continue for 4-5 days after neutrophil recovery (>500/mm3 ) • Minimum 2 weeks • Bacteraemia, deep tissue infection • After 2 weeks if remains neutropenic (< 500/mm3), BUT afebrile, no disease focus, mucous membranes, skin intact, no catheter site infection, no invasive procedures or ablative therapy planned…cease antibiotics and observe

More Related