A 48-year-old man, a kidney transplant recipient, is in the ICU for acute respiratory distress. He is intubated on mechanical ventilation and has a central venous catheter. His medications include tacrolimus and mycophenolate mofetil for immunosuppression and valganciclovir for CMV prophylaxis. Recent labs show WBC 1.2 × 10^3/mm^3 with an ANC of 350/mm^3 and platelets 210,000/mm^3. He is afebrile with no signs of infection, and cultures are pending. His tacrolimus trough is within the therapeutic range. Which of the following is the most appropriate first-line pharmacologic management?

A 48-year-old man, 10 days after orthotopic heart transplantation, is managed in the ICU. He remains intubated on assist-control ventilation, is receiving a continuous norepinephrine infusion via a central line, and is on broad-spectrum antibiotics for suspected ventilator-associated pneumonia. His immunosuppression includes tacrolimus, mycophenolate mofetil, and prednisone; he also received rabbit anti-thymocyte globulin (rATG) on post-operative days 0–2. Today, his absolute neutrophil count (ANC) is 350 cells/mm³ (previously 2,500 cells/mm³ on admission), with stable platelets and other labs. CMV and parvovirus B19 workup is pending. Which of the following is the most appropriate initial intervention?

A 45-year-old man, 6 months after kidney transplantation, is admitted to the ICU for severe sepsis. His current medications include tacrolimus (trough 25 ng/mL; target 8–12 ng/mL), mycophenolate mofetil, and valganciclovir prophylaxis. Laboratory tests reveal an absolute neutrophil count of 350/µL. His family reports that, due to financial constraints, he often skips doses early in the month and then takes extra doses when he obtains refills. Which of the following is the most critical initial action to address the precipitating risk factor for his neutropenia?

A 48-year-old man, 3 months post–kidney transplant, is in the ICU with septic shock. He is on pressure-control ventilation and a continuous norepinephrine infusion at 0.1 mcg/kg/min via a triple-lumen central venous catheter. His white blood cell count is 1.2 × 10³/mm³ with an absolute neutrophil count of 350/mm³. He is maintained on tacrolimus and mycophenolate mofetil; mycophenolate has been held for suspected drug-induced neutropenia and initiation of granulocyte colony-stimulating factor (G-CSF) is planned. Which of the following is the most appropriate method for administering G-CSF in this patient?

A 62-year-old man, 3 months post–kidney transplant, is admitted to the medical intensive care unit for respiratory distress. He is intubated, on mechanical ventilation, and receiving vasopressors via a central venous catheter. His current medications include tacrolimus, mycophenolate mofetil, prednisone, and valganciclovir for cytomegalovirus prophylaxis. Recent labs show a white blood cell count of 1.5 × 10³/mm³ with an absolute neutrophil count (ANC) of 450/mm³. His creatinine is stable, and an infectious workup is pending. Which of the following is the most appropriate initial intervention for this patient’s neutropenia?

A 45-year-old man with a recently diagnosed germ cell tumor is admitted to the ICU for acute hypoxemic respiratory failure. He completed his third cycle of bleomycin-containing chemotherapy 2 weeks ago. Over the past 48 hours, he developed progressive dyspnea and a nonproductive cough. On exam, T 38.1 °C, HR 110 bpm, BP 100/60 mm Hg, RR 30 breaths/min, SpO₂ 88% on room air. Arterial blood gas on room air shows pH 7.45, PaCO₂ 30 mm Hg, PaO₂ 55 mm Hg. Chest X-ray demonstrates new bilateral interstitial infiltrates. Pulmonary function tests before chemotherapy showed a mild reduction in DLCO. No new antibiotics, DMARDs, or antiarrhythmics have been started. Which of the following drugs is the most likely cause of his acute pulmonary deterioration?

A 62-year-old man, three months after kidney transplantation, is admitted to the ICU with acute respiratory distress requiring mechanical ventilation. He is on a continuous norepinephrine infusion for hemodynamic support. His baseline immunosuppression includes tacrolimus and mycophenolate mofetil; he also receives valganciclovir for CMV prophylaxis and trimethoprim–sulfamethoxazole (TMP–SMX) for Pneumocystis jirovecii prophylaxis. Over the past 24 hours, his white blood cell count has fallen to 1.8×10^3/mm^3 (baseline 6.5×10^3/mm^3), absolute neutrophil count to 450/mm^3 (baseline 4,000/mm^3), and platelets to 65,000/mm^3 (baseline 220,000/mm^3). Infectious workup is negative and there is no bleeding. Which of the following is the MOST appropriate initial pharmacotherapy adjustment to address the likely drug-induced cytopenias?

A 48-year-old man, 3 weeks post–kidney transplant, is admitted to the ICU for acute kidney injury. He is on assist-control ventilation and a continuous norepinephrine infusion via a central venous catheter. Over the past 48 hours his absolute neutrophil count has fallen from 1,800/mm³ to 350/mm³. He remains afebrile. His immunosuppressive regimen includes tacrolimus, mycophenolate mofetil, and valganciclovir for CMV prophylaxis. Which of the following is the most appropriate initial supportive care strategy to prevent infectious complications?

A 48-year-old man with a history of kidney transplantation (on tacrolimus, mycophenolate mofetil, and valganciclovir) is admitted to the medical ICU with septic shock due to pneumonia. He is intubated on assist-control ventilation and requires norepinephrine at 0.1 mcg/kg/min via a central line to maintain a MAP ≥65 mmHg. He is febrile to 39.5 °C, has a lactate of 4.8 mmol/L, and laboratory studies show WBC 0.8 × 10^3/µL (ANC 150 cells/µL). He has not yet received fluid resuscitation or empiric antibiotics. Which of the following is the most critical immediate priority?

A 48-year-old man, 3 months post–kidney transplant, is in the ICU for acute hypoxic respiratory failure and acute kidney injury requiring continuous renal replacement therapy (CRRT). He is intubated on assist-control ventilation and has a central venous catheter. His current medications include tacrolimus 4 mg PO BID, mycophenolate mofetil 1,000 mg PO BID, and valganciclovir 450 mg PO daily. Recent labs show WBC 1.2 × 10³/µL (4.5–11), ANC 350/µL (1.5–8.0), and a tacrolimus trough of 8.2 ng/mL (target 5–10). Blood cultures and viral panels are negative. Which of the following is the MOST appropriate initial pharmacotherapy adjustment to address his neutropenia?