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Neutropenic fever in cancer patients

Neutropenic fever in cancer patients

hayam
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Neutropenic fever in cancer patients

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  1. BY Dr. HAYAM FATEHY ABDELHAY GHAZY Lecturer of medical oncology Mansoura University OCMU FEBRILE NeutropeniA in Patients with Cancer

  2. Infection in the neutropenic patient has remained a major clinical challenge for over decades. While diagnostic and therapeutic interventions have improved greatly during this period, increases in the number of patients with neutropenia, changes in the etiologic agents involved, and growing antibiotic resistance have continued to be problematic

  3. Why is this an Oncologic emergency??

  4. 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 Infection + ABX + Immune system = cure

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

  6. ANC  500/mm3 or • 1000/mm3 and predicted decline to  500/mm Definition of Neutropenia

  7. (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) Absolute Neutrophil Count

  8. 0.7 X 1000 = 70040% =40/100=0.40 700 X 0.40 = 280 Calculation

  9. 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 Neutropenia

  10. 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 When Does Neutropenia Occur?

  11. What is the Risk?

  12. Bone Marrow Suppression

  13. Risk of Infection as Absolute Neutrophil Count Declines

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

  15. Changing etiology of bacteremia Viscoli et al, ClinInf Dis;40:S240-5 • Gram positive dominantsince 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-oesophagealcolonisation with GPC Epidemiology Gram negative resurgence

  16. < 7 days LOW risk • 7 to 14 days INTERMEDIATE RISK • > 14 days HIGH RISK Duration of Neutropenia

  17. < 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 • ~ patients with intermediate durations of neutropenia between 7 and 14 days had response rates of 79% Duration Of Neutropenia

  18. The mouth and throat • The skin • The gut • The lungs • The kidneys and bladder, especially with urinary catheter • At the site of a drip or central line An infection can occur anywhere in the body. The most common places are

  19. Initial management of febrile neutropenia Marti, F. M. et al. Ann Oncol2013 20:iv166-169iv; doi:10.1093/annonc/mdp163 (MASCC, Multinational Association for Supportive Care in Cancer)

  20. . MASCC Risk Index Factors and Weights MASCC, Multinational Association for Supportive Care in Cancer

  21. MASCC Risk Index Factors and Weights 1Burden of febrile neutropenia refers to general clinical status as influenced by the febrile neutropenic episode. It is evaluated in accordance with the following scale: no symptoms (5), mild symptoms (5), moderate symptoms (3), severe symptoms (0), moribund (0)(in a dying state; near death). 2Chronic obstructive pulmonary disease means active chronic bronchitis, emphysema, decrease in FEVs, need for oxygen therapy and/or steroids and/or bronchodilators.

  22. MASCC Risk Index Factors and Weights 3Previous fungal infection means demonstrated fungal infection or empirically treated suspected fungal infection. 4The points attributed to the variable "burden of febrile neutropenia"are not cumulative. Thus, the maximum theoretical score is therefore 26. A score of ≥ 21 is considered low risk and a score of < 21 as high risk (positive predictive value of 91%, specificity of 68%, and sensitivity of 71%). 

  23. Assessment of response and subsequent management Marti, F. M. et al. Ann Oncol2013 20:iv166-169iv; doi:10.1093/annonc/mdp163

  24. Gram-positivecocci 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 Common Microbes

  25. 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 functions of systems • Transfusions • Can cause fevers • Lines or catheters Initial evaluation

  26. ENT 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 ! Exam (be prepared to find no signs of inflammation)

  27. 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) Skin Exam- Ask the patient for any area of tenderness?

  28. 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 (/Foley Catheter) [- pyuria] -Stool Cultures and CDiff Toxin/PCR • Radiology -Chest Xray +/- CT abdomen/pelvis Febrile neutropeniaInvestigation

  29. 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. Lumbar puncture

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

  31. 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 , MRI of the spine or brain - more for evaluation of metastatic disease than FN IMAGING in FN

  32. 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 Stratify risk of complications

  33. •Prolonged Neutropenia (>14 days) • Haematological malignancy/ Allogenic HSCT • • Myelosuppresive chemotherapy • • Concurrent chemotherapy and radiotherapy • • Age >60 • • Co-morbidities eg. Diabetes, poor nutritional status. HIGH risk Patients

  34. • 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 HIGH risk Patients Continue……..

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

  36. treatment

  37. 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 ORAL vs IV

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

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

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

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

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

  43. Meningococcal Disease, Invasive Staphylococcus Aureus Infections, Drug resistant (MRSA, VISA, VRSA) Streptococcal Disease, Group A Invasive or Streptococcal TSS Streptococcal Disease, Invasive Group B Invasive Bacterial Diseases

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

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

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

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

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