syncytial virus (RSV) prophylaxis with RSV immunoglobulin (palivizumab) may be used in children younger than year on highly immunosuppressive regimens Approach to the Febrile Oncology Patient Definition of fever: Temperature >38 on two occasions separated by 1-2 hours or temperature re >38.5 one time Check CBC with differential: Does the patient have ANC < 500? Yes No t t Does the patient have a central line (CVL) ? Immediate blood culture and administration of broad-spectrum antibiotics* No Yes Y Obtain blood culture and consider administration of IV antibiotics ** ^' Pursue evaluation and management as dictated by signs and symptoms from history and physical examination 'Antibiotics used in Empiric Therapy of Febrile Neutropenia (Initial ED dosing ) • Standard Regimens • Cefepime 50 mg/kg IV (maximum dose 2,000 mg) • Ceftazidime 50 mg/kg IV (maximum dose 2,000 mg) • A semisynthetic penicillin with an aminoglycoside • Example: Piperacillin/tazobactam 75 mg/kg IV (maximum dose 4,500 mg) and Gentamicin 2.5 mg/kg IV • Cephalosporin and/or anaphylactic penicillin allergy • Clindamycin 13 mg/kg IV ( maximum dose 900 mg) and aztreonam 30 mg/kg IV (maximum dose 2,000 mg) "Options for management of Fever and non-Neutropenia in Patients with a CVL • Ceftriaxone 50 mg/kg IV ( maximum dose 2,000 mg) • Other institutional guidelines which may include no antibiotic therapy See text for considerations for additional coverage FIGURE 98.4 Management guidelines for the febrile oncology patient Risk assessment and management hinges substantially on whether the absolute neutrophil count (ANC) is below 500, whether the patient has localizing signs or symptoms, and whether an indwelling catheter is present Pediatric oncology patients are also at risk for common viral infections such as RSV, CMV, EBV, influenza, and adenovirus In general, the presentation of these infections is the same as in immunocompetent hosts Of note, primary varicella zoster infection can rapidly progress to a life-threatening infection in an immunocompromised patient Typhlitis, also known as neutropenic colitis, is a potentially life-threatening infection that occurs in patients with neutropenia and GI mucosal injury This infection occurs in the watershed regions of the cecum, appendix, and terminal ileum It is much more common in patients with advanced hematologic malignancies but can occur in patients with solid tumors Clostridium difficile colitis is relatively common in oncology patients due to treatment with broad-spectrum antibiotics that eradicates normal bowel flora Clinical Considerations Clinical Recognition In addition to sepsis, bacteremia, and soft tissue infections, the emergency clinician should consider additional infectious complications not commonly encountered in noncancer patients Initial symptoms of typhlitis can mimic appendicitis with periumbilical pain preceding right lower quadrant pain As the infection progresses, abdominal pain can become severe and examination findings include distention and persistent right lower quadrant tenderness C difficile colitis should be considered in patients with abdominal pain and diarrhea with or without abdominal distention Abdominal tenderness is generally minimal except in patients with very severe colitis Perirectal pain may be the presenting symptom of perirectal abscess/cellulitis Complaints of painful vesicular rash should raise concern for varicella infection Clinical Assessment Certain elements of the history can be very helpful Patients, family members, or referring oncologists may know if the patient is already neutropenic Specific questions to elicit any focal pain can direct the physical examination and empiric treatment decisions since this may be the only evidence of a localizing infection The presence of any indwelling devices such as a central line, ventriculoperitoneal shunt, or metal hardware used for bone tumors can also guide the differential diagnosis and/or empiric antibiotic coverage Since antibiotic allergies are common in this population, a thorough allergy history is critical The physical examination of the patient must be detailed and meticulous with careful attention paid to all mucocutaneous surfaces to elicit any focal tenderness, erythema, or edema, which may be slight Sites to examine include any central venous access devices at the skin entrance site, subcutaneous reservoirs, and along the subcutaneous line tract Nail beds on both fingers and toes should be carefully examined, and a thorough external rectal examination performed using circumferential palpation Do not perform a digital rectal examination or measure a rectal temperature as it may increase the risk of bacteremia Diagnostic testing should include a CBC with differential and blood cultures from all line lumens or via venipuncture in patients without a line Institution-specific guidelines should be followed regarding the need for peripheral blood cultures in addition to line cultures, and if additional orders or specimens are needed for anaerobic cultures Additional diagnostic testing can be obtained as needed after empiric antibiotics are started A chest x-ray should be obtained in patients with respiratory symptoms A urinalysis is not valuable for screening for infection since there are too few WBCs for the leukocyte esterase to be of value A urine culture should be obtained as long as it does not delay start of antibiotics or require catheterization, which may also increase the risk of bacteremia If the patient has a history of urinary tract infections, the risk of urinary catheterization may be justified Throat cultures may be of value if there are focal findings involving only the pharynx and/or tonsils but are rarely informative in a patient with diffuse mucositis Specific imaging may be of value based on physical findings Viral testing of vesicular lesions may identify varicella infections Cultures of draining abscesses or wounds may help guide antibiotic choice Diarrhea should be tested for C difficile toxin Management Antimicrobial treatment of suspected febrile neutropenia should be initiated within hour of patient arrival with the institutional standard regimen Therapy should be directed against both gram-positive and gram-negative organisms, including opportunistic pathogens ( Fig 98.4 ) Specific coverage, in addition to empiric therapy, is indicated for several clinical settings Third-generation cephalosporins may have inadequate gram-positive coverage for patients with soft tissue site infections and consideration should be given to a semisynthetic penicillin and an aminoglycoside or the addition of vancomycin, given the rising incidence of MRSA With evidence of sepsis, double coverage for gram-negative organisms may be added in addition to vancomycin to cover for possible Streptococcus viridans, especially in patients with advanced hematologic malignancies Fungal coverage is often considered for patients in shock Empiric antibiotics for suspected typhlitis include broad-spectrum coverage of gram-negative enteric flora as well as specific anaerobic coverage and should be started as soon as the diagnosis is suspected Typical regimens are a carbapenem alone or a combination regimen such as piperacillin/tazobactam with gentamicin or ceftazidime with metronidazole Laboratory studies should include coagulation studies and lactic acid, as well as CBC with differential and basic chemistries to assess hydration and renal function Uncontrolled coagulopathy and/or acidosis are consistent with necrotic bowel Serial abdominal x-rays should be performed to look for intramural air (pneumatosis), which is a hallmark of this diagnosis, or free air, which is an indication for surgery A CT scan of the abdomen can be useful for better delineation of the degree of bowel wall injury If CT scan is unavailable, ultrasound can show bowel wall thickening Early surgical consultation is appropriate Surgery itself is reserved for uncontrollable coagulopathy or acidosis as a consequence of bowel necrosis or evidence of perforation Treatment of confirmed or suspected C difficile colitis should include empiric vancomycin (oral) or metronidazole (parenteral or oral) Imaging is rarely useful, except in the most severe cases As soon as characteristic vesicles on an erythematous base are seen, empiric coverage for varicella should begin with acyclovir 10 mg/kg IV every hours in conjunction with appropriate hydration The patient should be assessed for pneumonitis with a careful respiratory examination, oxygen saturation, and a chest radiograph Liver enzymes should be measured for possible hepatic involvement All pediatric patients with fever and neutropenia less than 500 to 1,000 per μL should be admitted to the hospital unless there is an institutional management guideline that includes a specific follow-up plan for outpatient management of lowrisk fever and neutropenia See the Children’s Hospital of Philadelphia Clinical Pathway for Oncology Patient Presenting with Fever In the case of sepsis or septic shock, acute management as described in the Children’s Hospital of Philadelphia Severe Sepsis Clinical Pathway and Chapter 94 Infectious Diseases Emergencies should be followed for oncology patients, with the empiric antibiotic coverage described above for neutropenia Stress-dose steroids should be considered in patients who have received prolonged steroids recently either as part of cancer treatment or management of nausea and vomiting COMPLICATIONS OF CAR-T CELL THERAPY Goals of Treatment Some patients with refractory or relapsed ALL or B-cell lymphoma may have undergone treatment with chimeric antigen receptor modified T cells (CAR-T cell therapy) This approach genetically modifies autologous T cells to express a receptor which targets antigens on the surface of lymphoblasts Though not currently available in all centers, the early success of this therapy is likely to contribute to more widespread use Patients who have received CAR-T cell therapy are at risk for serious and potentially fatal complications, including TLS, cytokine release syndrome, and neurotoxicity ... Considerations Clinical Recognition In addition to sepsis, bacteremia, and soft tissue infections, the emergency clinician should consider additional infectious complications not commonly encountered... saturation, and a chest radiograph Liver enzymes should be measured for possible hepatic involvement All pediatric patients with fever and neutropenia less than 500 to 1,000 per μL should be admitted to