Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Febrile neutropenia by dr. dilip


Published on

Febrile neutropenia by Dr. Dilip choudhary, Department of Pediatrics, Mata Chanan Devi Hospital, New Delhi.

Published in: Health & Medicine
  • The recovery program is giving me the chance that I was seeking to change my life and to free me of the bulimia. For the first time in my life I feel that I am not alone trying to surpass my bulimia. I have real knowledges about my illness and how to beat them. I feel supported, pleased and liberated, with less fears and insecurities of my image. ♥♥♥
    Are you sure you want to  Yes  No
    Your message goes here
  • I have started the program this September and I must say I'm very pleased with the results. I was overweight and sick from candida and had severe swelling, and redness in the vulva area including vaginal discharge. Using your program I have lost a TON of weight. I no longer itch and scratch. The vaginal discharge had stopped and I'm feeling better than ever. I have also found through your book that some of my other health problems are from candida yeast overgrowth. My acid reflux and my skin texture had dramatically improved and I feel awesome physically. ♥♥♥
    Are you sure you want to  Yes  No
    Your message goes here
  • How I Cured My Candida, Life-long Sufferer Discovers, Powerful Secret To Yeast Infection Freedom ■■■
    Are you sure you want to  Yes  No
    Your message goes here
  • Great book! I'm on the second week and seeing definite improvement on my yeast infection symptoms. I must also note that the texture of my skin became very soft and consistent. I completely agree with many of your arguments in the book especially those about conventional methods for treating Yeast Infection. I wanted to let you know that I feel so fine you have no idea. I am not so tired all the time and I feel very energetic. The rashes on my neck and on the right side of my nose have also cleared up. I wish you all the health and happiness in the world and thanks so much for helping me. I really appreciate your time and efforts to assist me. 
    Are you sure you want to  Yes  No
    Your message goes here
  • Yeast Infection No More! Cure yeast infection, end your candida related symptoms and regain your natural inner balance ... Guaranteed! -- Discover how Linda Allen has taught thousands of people to achieve yeast infection freedom faster than they ever thought possible... Even if you've never succeeded at curing your candida before... Right here you've found the candida freedom success system you've been looking for! ▲▲▲
    Are you sure you want to  Yes  No
    Your message goes here

Febrile neutropenia by dr. dilip

  1. 1. Dr. Dilipkumar Choudhary Department of Pediatrics
  2. 2.  Definition- decrease in the number of absolute neutrophil count (ANC) in peripheral blood.  Absolute neutrophil count(ANC)= mature granulocytes + neutrophil band cells.  Neutrophil count must be stratified for age and race. • At birth  predominant but rapidly decrease in first few days of life. • Infancy  20-30% of TLC • At 5 yrs  equal number of neutrophils and lymphocytes count • In adults characteristic 70% predominance of neutrophils is usually attended during puberty.
  3. 3.  For white children lower limit of normal for ANC is 1500/ cu mm while  For black children its 1200/ cu mm.  Mild neutropenia - ANC 1000 - 1500/ cu mm  Moderate neutropenia – ANC 500 – 1000/ cu mm  Severe neutropenia – ANC <500/ cu mm  Agranulocytosis – ANC <200/ cu mm  Profound neutropenia – ANC<100/ cu mm  Prolonged neutropenia – lasting >7 days
  4. 4.  The relative lower limit of normal in blacks likely reflects the prevalence of the Duffy negative (Fy-/-) blood group, which is selectively enriched in populations in malaria belt of Africa and is associated with ANCs 200-600/ cu mm less than those who are Duffy positive.
  5. 5.  Development of fever in a neutropenic patient.  Defined as single oral/axillary temperature >38.3˚C (101˚F) or two consecutive temperature >38˚C (100˚F) in a 12 hr period for at least 1hr with ANC <500/cu mm or <1000 cu mm with expected decline to <500/cu mm during the next 48 hrs.
  6. 6.  Common in children on chemotherapy and the most common oncologic emergency.  The risk of infection is clearly increased when ANC drop below 1000/mm3, with a marked increase when the ANC is below 500/mm3.  Neutropenic patient can have serious life threatening infections even in the absence of fever and may not present with any localizing symptoms and signs of infection such as exudate, fluctuance and regional lymphadenopathy, sometimes only fever remain the only consistent early sign.
  7. 7.  Approximately 48 to 60% patients who become febrile have an established or occult infection.  Common sites of infection are the alimentary tract (i.e., mouth, pharynx, esophagus, large and small bowel and rectum), perirectal abscess, sinuses, throat, ear (otitis media), lungs and skin( cellulitis, furunculosis).  Catheter and IV sites are potential source of infection.
  8. 8. Gram positive bacteria -  Staphylococcus spp. (e.g. S. epidermidis and S. aureus)  Streptococcus spp. (alpha-hemolytic; e.g., S. mitis)  Enterococcus spp. (e.g. E. faecium, E. faecalis)  Clostridium spp. (C. difficile, C. septicum, C. tertium) Gram-negative bacteria-  Enterobacteriaceae (E. coli, Klebsiella spp., Enterobacter spp.)  Pseudomonas aeruginosa and  Stenotrophomonasmaltophilia  Anaerobes (e.g. Bacteroides spp. and Prevotella spp.)
  9. 9. Fungi-  Candida spp. (e.g. C. albicans, C. glabrata, C. tropicalis, C. krusei)  Aspergillus spp. (e.g. A. fumigatus, A. flavus, and A. terreus)  Fusarium spp. (e.g. F. solani and F. oxysporum)  Cryptococcus neoformans  Pneumocystis jiroveci (formerly, P. carinii)
  10. 10. Viruses-  Herpes simplex virus  Varicella-zoster virus  Cytomegalovirus  Parvovirus  Respiratory viruses
  11. 11. Potential causes of infection in patients with febrile neutropenia- Eyes Conjunctivitis, orbital cellulitis Ear, nose, throat Otitis media, sinusitis, tonsillitis pharyngitis, oral candidiasis Teeth Dental caries/abscess Chest Pneumonia Abdomen Diarrhea, dysentery, neutropenic- enterocolitis, pseudomembranous colitis Perineum Perianal candidiasis, perianal abscess Skin Cellulitis, abscess, nodular or target lesions suggestive of fungal infections, varicella rash, purpura fulminans CNS Meningitis, meningoencephalitis, cavernous sinus thrombosis Urinary tract Urinary tract infection Intravascular catheters Exit site infection, tunnel infection
  12. 12. History  Fever -onset, duration and severity  Associated localizing symptoms: Ear, nose, throat, respiratory, gastrointestinal tract, musculoskeletal and urinary system.  Phase of chemotherapy (intensive vs. non intensive)  Duration since the last chemotherapy  Recent hospitalization and antibiotics received, if any
  13. 13. Examination  Vitals- in every patient of suspected febrile neutropenia, the patient may appear well despite being in a state of hemodynamic compromise.  Detailed physical examination focusing on possible sites of infection must be undertaken. Sites that are commonly overlooked include oral cavity, ear, sinuses, skin, nails, perianal area, intravascular catheter insertion site and the site of bone marrow aspiration.
  14. 14. Investigations First line investigations- to be performed in every case (1).Complete blood count, including differential leukocyte count and ANC (2). Serum electrolytes, urea and creatinine (3). Blood culture: Obtain as early as possible and always before the administration of antibiotics. Two sets of blood cultures from separate venipuncture sites should ideally be drawn. In the presence of a central venous catheter, a blood culture should be obtained from each lumen of the catheter and another from peripheral vein. (4). Chest radiograph: mandatory for all, initial x-ray may be non informative but must be taken as a baseline for comparison with later films. (5). Cultures from any other site, as clinically relevant. This includes stool, urine, cerebrospinal fluid, skin, respiratory secretions or pus.
  15. 15. Second line investigations- Dictated by the clinical course: (1).CT scan of chest/paranasal sinuses may be indicated in patients with suspected fungal infection. (2).Bronchoalveolar lavage: If pneumonia is non-resolving/ non-responding. (3).Skin biopsy, from skin nodules, if any.  Despite advances in diagnostic methods, infection is documented only in 30-40% patients.
  16. 16. Risk stratification is crucial in determining the appropriate-  Choice of antimicrobials,  Route of administration (intravenous vs. oral),  Setting (inpatient vs. outpatient) and  Duration.  The patients can be classified as low or high risk
  17. 17. Low risk High risk Neutropenia expected to resolve in about 7 days Indicators: • Afebrile for 24hrs • Clinically well, hemodynamically stable • Sterile blood culture • Control of local infection • Evidence of bone marrow recovery with rising polymorphs count/ platelets/ ANC • Non-intensive phase of chemotherapy e.g., maintenance phase of chemotherapy • Malignancy in remission • ANC≥100/mm3 and likely to rise within the next 7 d. Neutropenia >7days Indicators • Fever persisting • Culture positive • No evidence of bone marrow recovery • Recent intensive chemotherapy • Profound neutropenia (ANC<100 cells/mm3), anticipated to extend for >7 d. • Evidence of hypotension, respiratory distress or hypoxemia. • Mucositis interfering with oral intake or resulting in diarrhea
  18. 18.  Presence of fever >39˚C, associated hypotension, ANC<100 cu mm, duration of neutropenia >7days  frequently associated with bacteremia.  Santolaya, et al found serum CRP more than 90 mg/L, hypotension, relapsed leukemia, platelet count less than 50,000/mm3 and recent chemotherapy to be useful predictors of serious bacterial infection.  Klaassen et al found an absolute monocyte count less than 100 cell/mm3, co-morbidity and abnormal chest radiograph to correlate with high risk for significant bacterial infection.  For adults- the Multinational Association of Supportive Care in Cancer (MASCC) score is used for risk stratification. Patient with score with ≥21 are at lower risk of complications.
  19. 19. General considerations-  Pro- active steps must be taken to reduce incidence of hospital acquired sepsis.  Barrier nursing practise- frequent hand washing, the use of alcohol based hand rub in between patients and wearing gloves must be ensured .  Use of IV fluids, central lines, foley’s catheter etc. must be restricted, if possible.
  20. 20.  Administration of IV fluids for minor reasons should be avoided.  Nasogastric feeding should be encouraged in patients with anorexia or mucositis.  Rectal enemas, suppositories, and rectal examinations are contraindicated in neutropenic patients  High-risk’ patients are to be hospitalized and administered broad-spectrum intravenous antibiotics  Empirical treatment should begin as soon as possible, even before the results of cultures are available.
  21. 21.  Important considerations during initial empirical therapy- • Risk stratification • Any focal signs and symptoms, site of infection (e.g., lung) • Antimicrobial susceptibilities of local pathogens • Recent hospitalization, recent antibiotic exposure or prophylactic drugs • Past history of infection (especially fungal or resistant bacterial such as ESBL or MRSA infection) • Most common potentially infecting organism based on type of immune defect • Co-morbid conditions.
  22. 22.  Care-takers are advised not to administer paracetamol at home as it may mask fever and can lead to delay in seeking medical care.  Administer the first dose of antibiotics without any delay. Delay in initiating antimicrobials significantly increases the morbidity and mortality.
  23. 23.  Anti-pseudomonal agents- penicillin (piperacillin-tazobactum), antipseudomonal cephalosporin (cefoperazone-sulbactum) or carbepenems (meropenem or imipenem-cilastatin) or cefepime is recommended as first line by Infectious Disease Society of America BUT no significant differences in treatment failure, including antibiotic modification, infection-related mortality, or adverse events were observed while comparing anti- pseudomonas penicillin± aminoglycoside regimen with carbapenem monotherapy in a recent meta analysis.
  24. 24.  Empirically  combination of antipseudomonal antibiotic (ceftazidime, cefaperazone/ salbactam) + an aminoglycoside is used as first line choice.  Switch to second line drugs: Vancomycin and Carbepenems (meropenem or imipenem-cilastatin) after 48–72 h, if fever is unrelenting and there is no improvement in the clinical condition.  Colistin- reserved as a third line drug.  If the cultures yield a specific pathogen, the regimen should be modified accordingly  For low risk FN  oral amoxicillin- clavulinate with ofloxacin OR cetrioxone with amikacin
  25. 25.  Indications for need of vancomycin in initial regimen if patient has - • Hypotension or evidence of septic shock • Obvious catheter related infection • H/O colonization with MRSA • High risk for viridans streptococci (severe mucositis/ AML / prior use of quinolone prophylaxis).  If indwelling line insitu or no response in 48 hrs  antistaphylococcal antibiotic should be added.  If fever persist for 4-5 days  antifungal (eg. Amphotericin B) should be added.  Discontinuation should always be kept in mind to minimize development of bacterial resistance
  26. 26. Add antistaphylococcal drug and if febrile at 4-5 days add antifungal Febrile neutropenia Initial evaluation Physical examination investigations Start treatment Ceftazidime + amynolycoside iv Monitor -Fever -ANC Febrile afetr48hrs Afebrile
  27. 27. Afebrile ANC>500/cu mm ANC<500/cu mm Low risk High risk Stop therapy when afebrile for >48hrs Switch to oral antibiotic Low risk High risk Give oral antibiotic for 7 days Continue antibiotic for 10-14 days
  28. 28.  If fever takes long to respond , the cultures are positive or ANC is <100/cu mm on admission antibiotics are given for 10-14 days or till ANC increases >500/cu mm.  P. jiroveci can cause pneumonia regardless of neutrophil count, prophylaxis with trimethoprim- sulfamethoxazole against PCP is an effective preventive strategy and should be provided to all children undergoing active treatment for malignancy.
  29. 29. Hematopoietic growth factor-  G-CSF (Filgrastim) @5mcg/kg/day in addition to antibiotics is useful in children with complicated febrile neutropenia (pneumonia, hypotension, invasive fungal infection or multi organ dysfunction), it results in- • more rapid neutrophil recovery • relatively fewer days of antibiotic use • Shortens length of hospital stay • Reduces mortality and morbidity But G-CSF has no role in the management of children with uncomplicated febrile neutropenia.
  30. 30. Thank you