FEBRILE NEUTROPENIA

(Fever in a Neutropenic Child) Fever in a neutropenic child is an emergency that needs urgent evaluation and institution of empirical antibiotic therapy, without waiting for a diagnosis.

Febrile neutropenia (FN) is generally defined as:

• Single oral temperature gt; 38.3°C (101°F)% or gt; 38°C sustained for gt; 1 hour,

• Absolute neutrophil count (ANC) lt; 500/mm³ or expected to drop below this level in next 24 hours.

Development of fever in a case with neutropenia due to any cause indicates possibility of serious underlying infections, though clinical signs may be masked due to paucity of inflammatory response. Risk of bacterial infection is inversely related to absolute neutrophil count.

Microbiologically, predominant infections in neutro­penic children are bacterial, including Staph. aureus (~50%), Pseudomonas (~20%) and anaerobic infections (~15%). While opportunistic viral, (e.g. CMV) and fungal infections are also common in these cases due to co-existing immunological defects, children with isolated neutropenia are not excessively prone to these infections. Clinical presentation of infections in neutropenic children is directly related to its severity:

• Mild neutropenia with absolute neurtrophil count gt;1000/ mm³, is generally well tolerated.

• Moderate neutropenia (500-1000 cells/mm³), may be asymptomatic or presents with mucositis, sino- pulmonary infections, fulminant skin/soft tissue infections and enterocolitis.

• Severe neutropenia (lt;500 cell/mm³) is frequently associated with generalized and potentially fatal infections, e.g. septicemia, pneumonia and visceral abscesses. Meningitis is unusual in neutropenic patients.

Disproportionately less signs of inflammation with minimal pus formation is an important feature of sepsis in neutropenic cases.

Diagnosis of infection in FN depends on microbial cultures from blood and potential sites for entry of infection, e.g. catheters or central lines. Serial neutrophil counts and inflammatory markers, e.g. CRP are necessary to assess the course of disease, along with investigation to search for focus of infection, e.g. chest skiagram, urine analysis, etc. and biochemical investigations for organ dysfunction.

Management aims to recognize infection in early stages and prevent rapid progression from bacteremia to septicemia to septic shock. Important steps include:

• Risk-assessment: All cases of FN must be classified as high-risk or low-risk for serious infections before deciding the line of management (Table 10.6).

• Management of high-risk FN: Children with high- risk FN need immediate hospitalization and initiation of empirical antibiotics within 60 minutes, without waiting for reports. Choice of empirical antibiotic therapy in them must include a broad-spectrum beta-lactam antibiotic with anti-pseudomonal cover, e.g. piperacillin-tazobactam (IV 300 mg/kg/day q8hr) or a fourth-generation cephalosporin, e.g. cefepime with/without tazobactam (IV 100 mg/kg/day q12hr) or a carbapenem, e.g. meropenem (120 mg/kg/day q8hr). Vancomycin (IV 45-60 mg/kg/day q8hr) must be added in clinically unstable patients with hypotension/shock or in those with (a) mucositis, (b) skin and soft-tissue infection, (c) central lines, (d) locally high MRSA prevalence.

These cases, specially if on steroids, should also be investigated for invasive fungal disease (IFD) and started on empirical antifungal therapy if fever persists for gt;96 hours with liposomal amphotericin B (IV 3-5 mg/kg/day) or Caspofungin (IV 70 mg/m² on day 1 followed by 50 mg/m²/day) empirical antifungal therapy may be stopped after resolution of fever, provided there is no feature suggestive of IFD.

*Hypotension, Hypoxia, Altered sensorium, Respiratory distress, Mucositis or Abdominal symptoms

HSCT: Hematopoietic stem cell transplant

• Management of low-risk FN: Low-risk FN may be treated on OPD basis with oral antibiotics, if patient is accepting well and can be monitored at home. Initial choice of antibiotics in these cases include a fluoroquinolone, e.g. ciprofloxacin (PO 20-30 mg/ kg/d q12hr) alone or in combination with amoxicillin- clavulanate (50-80 mg/kg/d q12hr). Same antibiotics may be given parenterally in a small child, vomiting or lack of compliance, after hospitalization.

• Supportive measures includes:

- Barrier nursing, hand hygiene, and strict asepsis.

- Nutritional support, either enteral with nasogastric tube, or parenteral, as required.

- Transfusions to maintain hemoglobin gt;8 g/dl and platelet count gt;20,000/mm³ #9632;

- Treatment of primary causes along with recombinant G-CSF therapy in severe/persistent neutropenia (Ch 19.8).

- Adequate pain relief with opioids should be pro­vided for mucositis, colitis, evolving abscess, or fissures. Paracetamol should be avoided in a FN child until it is clear that the criteria for starting antibiotics are fulfilled.

• How long to treat? Antibiotic therapy should conti­nue till the patient is afebrile for at least 48 hours, neutrophil counts rise gt;500 cells/mm³ and blood culture is sterile. Persistent of fever alone does not warrant change of antibiotics, which should be changed as per culture reports or in cases developing hemodynamic instability, fresh focus of infection or increase in inflammatory markers.

10.1.6