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Febrile neutropenia in chidren


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Febrile neutropenia in children by Dr. Saurav Kumar Upadhyay

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Febrile neutropenia in chidren

  1. 1. Topic presentation by: Dr. Saurav Kumar Upadhyay 1st Year, Junior resident Dept. of Pediatrics S.V.P. P.G.I.P. Cuttack
  2. 2. Neutropenia  Definition- decrease in the absolute number of circulating segmented neutrophils and band cells in peripheral blood  Absolute neutrophil count (ANC) = Total white blood cells/microL x percent (PMNs+band cells) ÷ 100  Neutrophil count must be stratified for age & race.  At birth- predominant but rapid decrease begins at 12 hour through the 1st wk of life.  Infancy- 20- 30% of TLC  At 5 years- equal number of neutrophils & lymphocytes count  In adults – characteristic 70% predominance of neutrophils is usually attained during puberty
  3. 3.  Constitutional neutropenia is neutropenia of longstanding duration, typically since childhood  For white children lower limit of normal for ANC is 1500/cu mm  For black children , it’s 1200/cu mm.
  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.  Chronic neutropenia is neutropenia that lasts more than three months  Mild neutropenia – ANC 1000 – 1500/cu mm  Moderate neutropenia – ANC 500 – 1000/cu mm  Severe neutropenia – ANC less than 500/cu mm  Agranulocytosis- ANC less than 200/cu mm  Profound neutropenia – ANC less than 100/cu mm  Prolonged neutropenia – lasting more than 7 days
  6. 6.  Cyclic neutropenia – Patients with chronic neutropenia since infancy and a history of recurrent fevers and chronic gingivitis should have WBC counts & DLC determined 3/wk for 6-8 wks to evaluate the periodicity suggestive of cyclic neutropenia. (oscillations ranging from Normal ANCs to <200/cu mm)  The term ‘‘Functional neutropenia’’ refers to patients whose hematologic malignancy results in qualitative defects (impaired phagocytosis and killing of pathogens) of circulating neutrophils. These patients should also be considered to be at increased risk for infection, despite a ‘‘normal’’ neutrophil count.
  7. 7.  Patients with neutropenia caused by increased destruction (e.g. autoimmune) may tolerate very low ANCs without increased frequency of infection.
  8. 8.  Severe congenital neutropenia :  Rare  Incidence 1-2 cases per 1 million population  Characterised by an arrest in maturation at the promyelocyte stage in the bone marrow, resulting in ANCs consistently < 200/cu mm  Autosomal Dominant form : mutations in the ELANE gene (60- 80% cases)  Autosomal Recessive form : mutations in HAX1 ( also known as Kostmann disease) or G6PC3 ( encoding a myeloid specific isoform of glucose-6-phosphatase)
  9. 9.  Infections associated with neutropenia:  Viral : CMV, Dengue, EBV, Hepatitis virus, HIV, Influenza, Measles, Parvo virus B19, Rubella, Varicella
  10. 10.  Bacterial : Anaplasma(formerly Ehrlichia), Brucella, Typhoid, Paratyhoid, Pertussis, TB (disseminated), Tularemia, any form of sepsis  Fungal : Histoplasmosis
  11. 11.  Protozoan : Malaria, Leishmaniasis  Rickettsial : Psittacosis, Rocky mountain spotted fever, Typhus, Rickettsial pox
  12. 12.  Drugs causing neutropenia :  Immunologic : Aminopyrine, Propylthiouracil, Penicillins  Toxic : Phenothiazines, Clozapine  Hypersensitivity : Phenytoin, Phenobarbital
  13. 13. Febrile neutropenia - Introduction  Development of fever in a neutropenic patient.  Defined as single oral/axillary temperature > 38.3 °C (101 °F) OR two consecutive temperature > 38 °C in a 12 hr period for at least 1 hr WITH ANC < 500/cu mm or < 1000/cu mm with expected decline to < 500/cu mm during the next 48 hours.
  14. 14.  Microbiologically documented infection – Neutropenic fever with a clinical focus of infection and an associated pathogen  Clinically documented infection – Neutropenic fever with a clinical focus (eg, cellulitis, pneumonia), but without the isolation of an associated pathogen.  Unexplained fever – Neutropenic fever with neither a clinical focus of infection nor an identified pathogen
  15. 15.  A persistent neutropenic fever is a febrile episode without defervescence after at least five days of initial empiric broad- spectrum antibacterial therapy in high-risk neutropenic patients or after at least two days in low-risk neutropenic patients.  A recrudescent neutropenic fever is a febrile episode that recurs following initial defervescence during a course of broad-spectrum antibacterial therapy
  16. 16.  Common in children who are on chemotherapy and the most common oncologic emergency.  Occurs in children diagnosed to have acute leukemia,lymphoma,solid tumor or aplastic anemia  It may result from underlying malignancy per se or typically due to effect of chemotherapy  The risk of infection is clearly increased when ANC drops below 1000/cu mm , with a marked increase when the ANC is below 500/cu mm.
  17. 17.  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.
  18. 18. Epidemiology  Fever occurs frequently during chemotherapy-induced neutropenia. 10%–50% of patients with solid tumors and 80% of those with hematologic malignancies will develop fever during >1 chemotherapy cycle associated with neutropenia.  Most patients will have no infectious etiology documented. Clinically documented infections occur in 20%–30% of febrile episodes. Common sites of tissue-based infection include the intestinal tract, lung, and skin. Bacteremia occurs in 10%–25% of all patients, with most episodes occurring in the setting of prolonged or profound neutropenia (ANC<100 neutrophils/cu mm)
  19. 19. Risk of Infection as Absolute Neutrophil Count Declines
  20. 20. Pathophysiology  Decreased production of neutrophils from the bone marrow.  Shift of circulating neutrophils to the vascular endothelium or tissues such as the spleen, termed "margination", which can occur with splenomegaly and/or hypersplenism. In addition to neutropenia, disruption of mucociliary barriers, extensive use of invasive devices and shifts in inherent microbial flora due to prolonged antimicrobial usage predispose these patients to infection. Besides these, qualitative defects in neutrophil function described in hematological malignancies also contribute to FN.
  21. 21.  Immune-mediated destruction : The current hypothesis of immune-mediated drug-induced agranulocytosis suggests that the drug, or more commonly a reactive metabolite of the drug, irreversibly binds to the neutrophil membrane. In some cases, the reactive metabolite results in the production of antibodies or T cells directed against the altered membrane structure; in others, true antineutrophil autoantibodies are produced that do not require the presence of the drug .  Direct toxic effects upon marrow granulocytic precursors : Some drugs can directly damage myeloid precursors. As an example, detoxification of many nonpolar compounds requires conversion to a chemically reactive intermediate that may bind to nuclear material or cytoplasmic proteins, causing direct toxicity
  22. 22. Common pathogens in febrile neutropenic children  Gram Positive Bacteria-  Staphylococcus species ( e.g. S. epidermidis & S. aureus)  Streptococcus species ( alpha hemolytic, e.g. S . mitis)  Enterococcus species ( e.g. E. faecium, E. faecalis)  Clostridium species ( C. difficile, C. septicum, C. tertium)  Gram Negative Bacteria-  Enterobacteriaceae ( E. coli, Klebsiella spp. , Enterobacter spp.)  Pseudomonas aeuroginosa  Stenotrophomonas maltophilia  Anaerobes (e.g. Bacteroides spp & Prevotella spp. )
  23. 23.  Fungi-  Candida spp. ( e.g. C. albicans, C. glabrata, C. tropicalis, C. krusei)  Aspergillus spp. ( e.g. A. fumigatus, A. flavus, A.terreus)  Fusarium spp. ( e.g. F. solani & F. oxysporum)  Cryptococcus neofrmans  Pneumocystis jiroveci ( formerly known as P. carinii)
  24. 24.  Viruses –  Herpes simplex virus  Varicella zoster virus  Cytomegalo virus  Parvo virus  Respiratory viruses
  25. 25.  Potential sites 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, Meningo encephalitis, Cavernous sinus thrombosis  Urinary tract Urinary tract infection  Intravascular catheters Exit site infection, Tunnel infection
  26. 26. System specific infections  Skin specific :  While cellulitis caused by Streptococcus or Staphylococci is common, neutropenic patients ,i.e. with ANC < 500/cu mm may develop infections with unusual organisms.  Innocent looking macules may be the first sign of bacterial or fungal sepsis. Signs of infection , e.g. purulence are often lacking.  It may progress rapidly to ecthyma gangrenosum which is localised in non pressure areas. It is often associated with Pseudomonas aeuroginosa bacteremia but may be caused by other bacteria.
  27. 27.  Debridement to prevent spread sometimes necessary early in the course of disease but can be performed after chemotherapy when the ANC increases.  Candidemia is also associated with a variety of skin conditions and commonly presents as a maculopapular rash. Punch biopsy of the skin may be the best method for diagnosis.  Cytokines , used adjuvants or primary treatments for cancer , can themselves cause rashes, complicating the differential diagnosis
  28. 28.  GI tract specific:  Upper GIT : Mouth ulcerations afflict most patients receiving chemotherapy and often associated with viridans streptococcal bacteremia.  Use of Keratinocyte growth factor ( Palifermin ) in a dose of 60 mcg/kg for 3 days before chemotherapy and total body irradiation is of proven value in preventing mucosal ulcerations after stem cell transplantation.
  29. 29.  Fluconazole is effective in the treatment of both local infections (thrush) and systemic infections ( esophagitis ) due to candida albicans.  Newer azoles are similarly effective.  Viruses, particularly HSV are a prominent cause of morbidity in immunocompromised patients, in whom they cause severe mucositis. Use of Acyclovir , either prophylacticaly or therapeuticaly, is of value.
  30. 30. Lower GIT: Hepatic candidiasis results from seeding of the liver ( usually from a GI source ) in neutropenic patients. Most common in patients treated for acute leukemia and usually presents around the time the neutropenia resolves.  Characteristic picture : persistent fever unresponsive to antibiotics, abdominal pain and tenderness or nausea and elevated levels of serum alkaline phosphatase in a patient with hematologic malignancy who has recently recovered from neutropenia.  Hepatic USG or CT may reveal bull’s eye lesions. In some cases , MRI reveals small lesions not visible by other imaging modalities.
  31. 31. Neutropenic Enterocolitis or Typhilitis  Also known as necrotising colitis, necrotising enteropathy, ileocecal syndrome & cecitis.  Inflammatory process involving colon and/or small bowel  Ischemia, necrosis, bacteremia  Hemorrhage, and perforation.  Fever and abdominal pain ( typically RLQ).  Diarrhea (often bloody)  Bowel wall thickening on ultrasonography or CT imaging, MRI  Common among patients with AML or ALL than among those with other types of cancer
  32. 32.  Treatment : Initial conservative management  bowel rest,  intravenous fluids,  TPN,  broad-spectrum antibiotics  and normalization of neutrophil counts.  Surgical intervention  obstruction, perforation, persistent gastrointestinal bleeding despite correction of thrombocytopenia and coagulopathy, and clinical deterioration.
  33. 33.  Pulmonary specific:  Pneumonia in immunocompromised patients may be difficult to diagnose because conventional methods of diagnosis depend on the presence of neutrophils.  Bacterial pneumonia in neutropenic patients may present without purulent sputum or, in fact, without any sputum at all- and may not produce physical findings suggestive of chest consolidation (rales or egophony).
  34. 34.  Aspergillus spp. can colonise the skin and respiratory tract or cause fatal systemic illness. In neutropenic patients, A. flavus or A. fumigatus can invade the blood vessels. Likely to present as a thrombotic or embolic event.  Aspergillus infection often present with pleuritic chest pain & fever. Hemoptysis may be an omnious sign. Chest X-ray may reveal new focal infiltrates or nodules. Chest CT may reveal a characteristic halo consisting of a mass-like infiltrate surrounded by an area of low attenuation. Presence of “ crescent sign” on a chest X-ray or CT scan suggest invasive Aspergillus infection.
  35. 35.  Endocrine specific:  Candida infection of the thyroid may be difficult to diagnose during the neutropenic period. Can be defined by indium-labelled WBC scans or gallium scans after neutrophil counts increase.  CMV infection can cause adrenalitis with or without resulting adrenal insufficiency.  Renal & ureteral infections:  Candida, which has a predilection for the kidney, can invade either from the blood stream or in a retrograde manner via the ureters or bladder in immunocompromised patients.
  36. 36. Evaluation  History  Fever – Onset, duration, severity  Associated localizing symptoms : Ear, Nose, Throat, Respiratory tract, Gastrointestinal tract, Musculoskeletal , CNS, Urinary system  Phase of chemotherapy ( Intensive vs. non intensive)  Duration since last chemotherapy  Recent hospitalisation and antibiotics received
  37. 37.  Examination  Vitals- in every patient of suspected febrile neutropenia is very important. 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 sites and the site of bone marrow aspiration.
  38. 38.  Investigations  First line investigations- to be performed in every cases. 1. Complete blood count including Differential Leucocyte count and ANC. 2. Serum electrolytes 3. Blood urea & Serum Creatinine 4. Blood cultue & sensitivity : obtain as early as possible and always before the adminstration of antibiotics. Two sets of blood culture from separate venipuncture sites should ideally be drawn. In the presence of central venous catheter, a blood culture should be obtained from each lumen of the catheter and another from peripheral vein.
  39. 39. 5. Cultures from any other site, as clinically relevant. This includes stool, urine, cerebrospinal fluid, skin, respiratory secretions or pus. 6. Chest radiograph: mandatory for all. Initial x-ray may be non informative but must be taken as a baseline for comparison with later films.
  40. 40.  Second line investigations- Dictated by clinical course. 1. Serum Galactomannan test & CT scan of chest/ paranasal sinuses may be indicated in patients with suspected fungal infection. Do not order CT scan in a neutropenic patient with a normal CXR initially. 2. In clinical practice if patient remains febrile for 3 to 5 days then the next step is HRCT. ( 50 % of patients with positive imaging have a normal CXR ) 3. Bronchoalveolar lavage : If Pneumonia is non- resolving/ non responding. Should be cultured for Mycoplasma, Chlamydophilia, Legionella, Nocardia, more common bacerial pathogens, and fungi.
  41. 41. 4. CT abdomen for Necrotizing Enterocolitis or Typhilitis 5. CT brain R/o ICH / MRI of the spine or brain - more for evaluation of metastatic disease than FN. 6. 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. 7. Skin biopsy, from skin nodules, if any
  42. 42.  Approach if ANC < 1000/ cu mm  Repeat blood counts in 3-4 wks  Serology and cultures for infectious agents  Discontinue drugs associated with neutropenia  Test for antineutrophil antibodies  Measure quantitative Ig (G,A and M), lymphocyte subsets
  43. 43.  Approach if ANC< 500/cu mm on 3 separate tests  Bone marrow aspiration & biopsy, with cytogenetics  Glucocorticoid stimulation test  Serial CBCs (3/wk for 6 wks)  Exocrine pancreatic functions  Skeletal radiographs
  44. 44.  Microbiology -Blood cultures (peripheral and all central line lumens) -Oral ulcers or sores –send swabs -Exit site swabs -Wound swabs -Urine Cultures -Stool Cultures and CDiff Toxin/PCR Paediatric patients weighing <40 kg, proportionately smaller volumes of blood culture samples are suggested. Some centres limit blood draws to no more than 1% of a patient’s total blood volume. Because total blood volume is approximately 70ml/kg, the total sample limit would be 7 ml for a 10-kg patient and 28 ml for a 40-kg patient. Despite advances in diagnostic methods, infection is documented only in 30 - 40% patients.
  45. 45. Risk stratification  Risk stratification is crucial in determining the appropriate  Choice of antimicrobials  Route of administration ( IV or Oral )  Setting ( inpatient vs. outpatient )  Duration of treatment  The patient can be classified as low or high risk.
  46. 46. Risk assessment Low risk High risk  Neutropenia is expected to resolve in about 7 days.  Indicators:  Afebrile for 24 hours, Temperature <39˚ C  Clinically well, haemodynamically stable  Sterile blood culture  Lack of any focus of infection, eg: pneumonia,abscess, sinusitis or diarrhoea  Lack of medical comorbidities  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/ cu mm and likely to rise within the next 7 days.  Absolute monocyte count > 100/mm3  Neutropenia > 7 days  Indicators:  Fever persisting  Culture positive  Any focus of infection,eg: cellulitis, abscess, pnemonia, diarrhoea  No evidence of bone marrow recovery  Recent intensive chemotherapy  Profound neutropenia ( ANC < 100/cu mm ) anticipated to extend for > 7 days  Evidence of hypotension, respiratory distress or hypoxemia.  Mucositis interfering with oral intake or resulting in diarrhea.
  47. 47.  Presence of fever > 39 ° c, associated with hypotension, ANC < 100/ cu mm, duration of neutropenia > 7 days are frequently associated with bacteremia.  Studies have found that serum CRP more than 90 mg/ L , hypotension, relapsed leukemia, platelet count <50,000/cu mm and recent chemotherapy are useful predictors of serious bacterial infection.  Studies have found that an absolute monocyte count <100/ cu mm, co-morbidity and abnormal chest radiograph correlate with high risk for bacterial infection.
  48. 48.  Risk scoring :  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 complication.  Clinical Index of Stable Febrile Neutropenia (CISNE)
  49. 49. The Multinational Association for Supportive Care in Cancer Risk-Index Score (The American Society for Clinical Oncology)  Criteria --------------------------------------------------------Score  Burden of illness(no/mild)----------------------------------5  Burden of illness(moderate)---------------------------------3  Burden of illness (sever)--------------------------------------0  No Hypotension ----------------------------------------------5  No COPD-------------------------------------------------------4  Solid Tumor/ Lymphoma, no previous Fungal infection-------------------------------4  No Dehydration------------------------------------------------3  Outpatient Status (onset of fever)---------------------------3  Age < 60 years--------------------------------------------------2
  50. 50. Clinical Index of Stable Febrile Neutropenia (CISNE)  Specific of patients with solid tumors and seemingly stable episodes.  Able to discriminate patients who are at low, intermediate & high risk of complications  With CISNE scoring, the complication rate was determined to be 1.1% for low risk patients, 6.2% for intermediate risk patients and 36% for high risk patients.  Prime purpose of this scoring is to avoid complications from an early hospital release.
  51. 51. Management  IV MONO THERAPY  IV DUAL THERAPY  COMBINATION THERAPY Mono or dual therapy + VANCOMYCIN
  52. 52.  Anti-pseudomonal β-lactam agents:  Monotherapy with anti-pseudomonal β-lactam agents such as anti-pseudomonas penicillin(Piperacillin-tazobactum), anti-pseudomonal cephalosporin(Cefoperazone- sulbactum) or carbapenems(Meropenem or Imipinem- cilastatin) or Cefepime is recommended as first line by Infectious Disease Society of America.  Carbapenems can be reserved as second line antibiotics to prevent the emergence of drug resistant organisms.  Colistin is reserved as third line drug.
  53. 53. 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 Carbepenem monotherapy in a recent meta analysis.
  54. 54.  Empirically, combination of antipseudomonal antibiotic (Ceftazidime, Cefoperazone -sulbactum) + an Aminoglycoside is used as First line of defence.  Swich to second line drugs : Vancomycin and Carbepenems (Meropenem, Imipenem- Cilastatin) after 48- 72 hours, if fever is unrelenting and there is no improvement in clinical condition.  If the culture yields a specific pathogen, the regimen should be modified aacordingly.  For low risk patients, oral Amoxicillin- Clavulinate with Ofloxacin OR Ceftriaxone with Amikacin combiation is preffered.
  55. 55. Indications for need of Vancomycin in initial regimen if patient has  Hypotension or evidence of septic shock.  Obvious catheter related infection  H/O colonisation with MRSA  High risk for viridans Streptococci (severe mucositis/ AML / prior use of Quinolone prophylaxis)  If indwelling line in situ or no response in 48 hours → antistaphylococcal antibiotic should be added.  Radiographically confirmed pneumonia
  56. 56.  In hemodynamically unstable patient, an adequate coverage for drug resistant gram negative & gram positive organisms as well as for anaerobes should be given. Hence, second line drugs should be administered upfront.  Combination of anti-pseudomonal carbapenem, as well as addition of an aminoglycoside, together with vancomycin provides this cover.
  57. 57.  Emperical or presumptive anti-malarial therapy is not recommended. • Consideration in antibiotics selection in case of organ dysfunction- (renal and liver) Cisplatin, amphotericin B, cyclosporine, vancomycin, and aminoglycosides should be avoided in combination.  If fever persists for 4-5 days→ antifungal ( e.g. Amphotericin B ) should be added.  Discontinuation should always be kept in mind to minimise development of bacterial resistance.
  58. 58. Antibiotic stopping guide  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, mucus membranes, skin intact, no catheter site infection, no invasive procedures or ablative therapy planned…. Cease antibiotics and observe. -
  59. 59. Duration Of Neutropenia and response rates to therapy  < 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%
  60. 60. PERSISTENT FEVER (When temperatures do not go away) Evaluate for source of persistent fever  Resistant pathogen or slow response to therapy  Emergence of second infection (overgrowth, superinfection, nosocomial infection)  Inadequate serum or tissue level of antibiotic(s)  Drug fever  Abscess, obstruction, foreign body infection
  62. 62. Role of Empirical or Pre-emptive Antifungal therapy  Candida species are the most common fungal pathogens during neutropenia, typically occurring during neutropenic episodes lasting > 1 week, and Aspergillus species are less common, usually occurring with prolonged neutropenia lasting > 2–3 weeks  Past studies have shown that use of empiric antifungal therapy in neutropenic patients with persistent fever reduced mortality compared with patients who did not receive empiric antifungal therapy
  63. 63.  Until recently, Amphotericin B was the drug of choice for febrile neutropenia not responding to broad-spectrum antibiotics .  A small study comparing Itraconazole and AmphotericinB demonstrated higher rates of clinical success (composite of defervescence, absence of breakthrough fungal infections, and absence of adverse drug events) with itraconazole.  Voriconazole , a second-generation triazole with an extended spectrum that includes molds.
  64. 64. Other Therapies  Antiviral drugs  No indication for empirical use of antiviral agents  Treat HSV or VZV lesions  Consider acyclovir (famiciclovir or valacyclovir) for suppression of HSV.
  65. 65. Other Therapies  Granulocyte transfusions  Not routine  Consider with profound neutropenia, dysfunctional neutrophils and failure to control bacterial infection despite optimal antibiotics and G-CSF, and for severe uncontrollable fungal infections.  1 unit contains 1 1010 granulocytes  Rate : 10 to 15 mL/kg . May be repeated after 12 to 24 hrs
  66. 66.  Hematopoietic growth factor:  G-CSF (Filgrastim) @ 2-5mcg/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 hospial stay. - reduces mortality and morbidity. But G-CSF has no role in the management of children with uncomplicated neutropenia.
  67. 67. MYELOID RECONSTITUTION SYNDROME  Clinicians should be aware of the myeloid reconstitution syndrome, in which there may be onset or progression of an inflammatory focus defined clinically or radiologically that manifests at the time of neutrophil recovery.  Because such processes appear in the context of a persistent neutropenic fever syndrome, the likelihood of superinfection must be considered with respect to the antimicrobial spectrum of the patient’s current empiric antibacterial therapy.
  68. 68. Approach to catheter infections in immunocompromised patients
  69. 69.  General considerations  Pro active steps must be taken to reduce incidence of hospital acquired sepsis  Barrier nursing practice – frequent hand washing, the use alcohol based hand rub in between patients and wearing gloves must be ensured.  Use of IV fluids, central lines, foley’s catheter et. Must be restricted, if possible.  Care-takers are advised not to administer paracetamol at home as it may mask fever and can delay in seeking medical care.
  70. 70.  Adminstration of IV fluids for minor reasons should be avoided.  Nasogatric feeding should be encouraged in patients with anorexia or mucositis.  Rectal enema, suppositories and rectal examinations are contraindicated in neutropenic patients.  High risk patients are to be hospitalised and administered broad spectrum intravenous antibiotics.  Empirical treatment should begin as soon as possible, even before the results of culture are available.  Knowledge of locally prevailing bacteriological profile & antimicrobial susceptibility data is crucial for choice of antibiotics
  71. 71.  Non-invasive intermittent positive pressure ventilation should be attempted in case of acute respiratory failure.  Hemoglobin < 8g/dl is generally an indication for blood transfusion in a stable patient.  Indication for platelet transfusion: in a stable patient without any comorbidities and bleeds, prophylactic transfusions are recommended at a count below 10000. Transfusion threshold of 20000 recommended in patients with minor bleeds(mucosal,epistaxis) and 1,00,000 in major bleeds(hemoptysis, GI, or CNS bleeds)
  72. 72.  P. jiroveci can cause pneumonia regardless of neutrophil count. Prophylaxis with Trimethoprim- Sulphamethoxazole against PCP is an effective preventive strategy and should be provided to all children undergoing active treatment for malignancy.  Clinicians recommend giving splenoctomised patients a small supply of antibiotics effective against S. pneumoniae, N. meningitidis and H. inflenzae to avert rapid, overwhelming sepsis in the event that they can not present for medical attention immediately after the onset of fever or other symptoms of bacterial infection. A few Amoxicillin/Clavulanic acid tablets are a reasonable choice for this purpose.
  73. 73. Vaccination of cancer patients receiving chemotherapy