A 65-year-old male is admitted to the hospital with malaise and fatigue for the past week. His WBC count on admission was 27 000 cells/mL. The patient was ultimately diagnosed with high-grade acute promyelocytic leukemia. A tunneled central venous catheter was placed and the patient was started on all-trans-retinoic acid, daunorubicin, and cytarabine. Four days after initiation of chemotherapy, he developed a fever of 39.1°C (102.3°F) and altered mental status. His blood pressure was 90/54 mm Hg, heart rate 108 beats per minute, respiratory rate 24 breaths per minute, and oxygen saturation 94% on 5 L of supplemental oxygen. Laboratory evaluation was significant for neutropenia (absolute neutrophil count 300 cells/µL). His chest x-ray showed a focal consolidation in the right middle lobe. He was admitted to the intensive care unit and blood cultures were obtained.
What is the BEST empiric intravenous antibiotic regimen for this patient?A. Ciprofloxacin and ampicillin-sulbactam
Correct Answer: D
Neutropenia can be seen in varying degrees. Mild neutropenia is defined as an absolute neutrophil count (ANC) <1 500 cells/µL, while moderate neutropenia requires an ANC <1 000 cells/µL and severe neutropenia requires an ANC <500 cells/µL or an ANC that is expected to decrease to <500 cells/µL over the next 48 hours. Profound neutropenia is defined by an ANC <100 cells/µL. Fever in neutropenic patients is defined as a single oral temperature of 38.3°C (101°F) or a temperature of 38.0°C (100.4°F) sustained over 1 hour. Patients with prolonged (>7 days) and profound neutropenia are at high risk for complications such as hypotension and inhospital mortality.
Infections in neutropenic patients are presumed to arise from patient’s existent bacterial flora. Although common sites of infection include the skin, lungs, and intestinal tract, the majority of febrile neutropenia episodes do not have an identifiable source of infection.
Empiric antibiotics should be initiated within 120 minutes of patient presentation. Blood cultures should be drawn preferably before antibiotics are initiated. Empiric antimicrobial therapy should include an antipseudomonal beta-lactam agent (cefepime, piperacillin-tazobactam, or a carbapenem). Aminoglycosides and fluoroquinolones may be added as an additional anti-pseudomonal agent. Vancomycin should be added if pneumonia, skin and soft tissue infection, or central venous catheter infection is clinically suspected. Hemodynamic instability is another indication for the addition of vancomycin to a neutropenic patient’s initial regimen. Empiric antifungal therapy is only considered in those patients who are persistently febrile and neutropenic on empiric antibacterial therapy for at least 4 days. Candida species–related infections are commonly seen after the first week and mold infections such as aspergillosis are seen after 2 weeks of persistent neutropenia. In our patient, pneumonia and central venous catheter infection are diagnostic considerations meriting vancomycin in addition to piperacillintazobactam for empiric antimicrobial therapy.