Historically, the majority of infections were due to gram-negative bacteria, although recently there has been an increase in documented gram-positive infections. Empiric coverage should follow local hospital guidelines, which take into account institutional prevalence of drug-resistant microbes. Antipseudomonal activity is mandatory. In general, empiric IV monotherapy with ceftazidime, piperacillin/tazobactam, or meropenem are recommended. The tendency now is to avoid aminoglycosides because of potential nephrotoxicity, but the addition of a split-dose aminoglycoside may be appropriate in patients with previously documented multidrug-resistant pseudomonas or suspected meningitis or endocarditis. Drugs targeting staphylococcus, like vancomycin, linezolid, or daptomycin, are not routinely added but may be considered if a catheter-related infection or cutaneous infection with methicillin-resistant Staphylococcus aureus (MRSA) is likely or if periorbital cellulitis is present. While most patients will be admitted to the hospital for IV antibiotics and close observation, low-risk patients can be treated as outpatients with oral combinations such as ciprofloxacin 750 mg orally twice a day with amoxicillin/clavulin 875/125 mg orally twice a day, provided the following conditions are fulfilled: quinolone prophylaxis was not employed, the patient was not hospitalized at the time fever initially developed, there is no associated acute or poorly controlled comorbidity, renal and liver function are good and stable, pneumonia or other complex infections are unlikely, mucositis is mild and the patient can tolerate oral medication, mental status is lucid and no new neurologic symptoms are present, hemodynamics and oxygenation are normal, alemtuzumab treatment was not employed, the malignancy is basically controlled, the anticipated duration of severe neutropenia is shorter than seven days, the patient has good performance status, and he or she lives less than one hour from the hospital and has a telephone from which to dial emergency medical services. Ideally, the patient would also live with a responsible adult who can keep an eye on him or her and call emergency medical services or the treating physician should the patient's condition deteriorate. The Multinational Association for Supportive Care in Cancer (MASCC) risk index may also be used to assess the advisability of treating febrile neutropenia in the outpatient setting.