febrile neutropenia in chidren

Topic presentation by: Dr. Saurav Kumar Upadhyay1st Year, Junior resident

Dept. of PediatricsS.V.P. P.G.I.P. Cuttack

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

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.

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.

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

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.

Patients with neutropenia caused by increased destruction (e.g. autoimmune) may tolerate very low ANCs without increased frequency of infection.

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)

Infections associated with neutropenia:

Viral : CMV,

Dengue,

EBV,

Hepatitis virus,

HIV,

Influenza,

Measles,

Parvo virus B19,

Rubella,

Varicella

Bacterial : Anaplasma(formerly Ehrlichia),

Brucella,

Typhoid,

Paratyhoid,

Pertussis,

TB (disseminated),

Tularemia,

any form of sepsis

Fungal : Histoplasmosis

Protozoan : Malaria,

Leishmaniasis

Rickettsial : Psittacosis,

Rocky mountain spotted fever,

Typhus,

Rickettsial pox

Drugs causing neutropenia :

Immunologic : Aminopyrine, Propylthiouracil, Penicillins

Toxic : Phenothiazines, Clozapine

Hypersensitivity : Phenytoin, Phenobarbital

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.

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

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 neutropenicpatients or after at least two days in low-risk neutropenicpatients.

A recrudescent neutropenic fever is a febrile episode that recurs following initial defervescence during a course of broad-spectrum antibacterial therapy

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.

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.

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)

Risk of Infection as Absolute NeutrophilCount Declines

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.

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 neutrophilmembrane. 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 autoantibodiesare 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

Common pathogens in febrile neutropenicchildren 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. )

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)

Viruses – Herpes simplex virus

Varicella zoster virus

Cytomegalo virus

Parvo virus

Respiratory viruses

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

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.

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

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.

Fluconazole is effective in the treatment of both local infections (thrush) and systemic infections ( esophagitis ) due to candidaalbicans.

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.

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.

Neutropenic Enterocolitis or Typhilitis

Also known as necrotising colitis, necrotising enteropathy, ileocecalsyndrome & 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

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.

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).

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.

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.

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

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 , perianalarea, intravascular catheter insertion sites and the site of bone marrow aspiration.

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.

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.

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.

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

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

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

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.

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.

Risk assessmentLow 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.

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.

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)

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

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.

Management IV MONO THERAPY

IV DUAL THERAPY

COMBINATION THERAPY

Mono or dual therapy + VANCOMYCIN

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.

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.

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 OfloxacinOR Ceftriaxone with Amikacin combiation is preffered.

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

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.

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 minimisedevelopment of bacterial resistance.

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.

-

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 neutropeniabetween 7 and 14 days had response rates of 79%

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

IDSA GUIDELINES

Role of Empirical or Pre-emptive Antifungal therapy

Candida species are the most common fungal pathogens duringneutropenia, typically occurring during neutropenic episodeslasting > 1 week, and Aspergillus species are less common,usually occurring with prolonged neutropenia lasting > 2–3weeks

Past studies have shown that use of empiric antifungal therapy inneutropenic patients with persistent fever reduced mortalitycompared with patients who did not receive empiric antifungaltherapy

Until recently, Amphotericin B was the drug of choice for febrile neutropenia not responding to broad-spectrum antibiotics .

A small study comparing Itraconazole and AmphotericinBdemonstrated higher rates of clinical success (composite ofdefervescence, absence of breakthrough fungal infections, andabsence of adverse drug events) with itraconazole.

Voriconazole , a second-generation triazole with an extendedspectrum that includes molds.

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.

Other Therapies Granulocyte transfusions

Not routine

Consider with profound neutropenia, dysfunctionalneutrophils and failure to control bacterial infection despiteoptimal antibiotics and G-CSF, and for severe uncontrollablefungal infections.

1 unit contains 1 1010 granulocytes

Rate : 10 to 15 mL/kg . May be repeated after 12 to 24 hrs

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.

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 superinfectionmust be considered with respect to the antimicrobial spectrum of the patient’s current empiric antibacterial therapy.

Approach to catheter infections in immunocompromisedpatients

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.

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

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)

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.

Vaccination of cancer patients receiving chemotherapy