A 24-year-old man with cystic fibrosis has a history of recurrent pulmonary infections, bronchiectasis, pancreatic insufficiency, and elevated sweat chloride levels. Which of the following best describes the genetic basis of cystic fibrosis and its primary physiological consequence?

A 28-year-old male (weight 70 kg) with cystic fibrosis is admitted to the ICU for an acute pulmonary exacerbation. He is intubated on assist-control ventilation and receiving continuous vasopressor support via a central venous catheter. His current antibiotics are meropenem 1 g IV every 8 hours and tobramycin 10 mg/kg (700 mg) IV every 24 hours. Therapeutic drug monitoring shows a tobramycin peak of 28 mcg/mL (target 20–30 mcg/mL) and trough of 1.8 mcg/mL (target <1 mcg/mL). Baseline creatinine was 0.8 mg/dL but has risen to 1.5 mg/dL over 48 hours, with decreased urine output. Sputum cultures grow Pseudomonas aeruginosa susceptible to both agents. Which of the following is the most appropriate adjustment to his tobramycin regimen?

A 25-year-old female with cystic fibrosis is hospitalized for an acute pulmonary exacerbation characterized by increased cough, thick tenacious sputum, and worsening dyspnea requiring supplemental oxygen. To reduce the viscosity of her airway secretions, which pharmacologic agent acts by enzymatically cleaving extracellular DNA within the mucus?

A 28-year-old man with cystic fibrosis (CF) (height 1.75 m, weight 68 kg) is admitted to the ICU for an acute pulmonary exacerbation. He has been on high-flow nasal cannula (HFNC) oxygen at 60 L/min and FiO₂ 80% for the past 2 hours but remains in significant respiratory distress. Vitals: HR 115 bpm, BP 105/60 mmHg, RR 38 breaths/min, SpO₂ 88% on current settings. Arterial blood gas shows pH 7.25, PaCO₂ 70 mmHg, PaO₂ 55 mmHg, HCO₃⁻ 28 mEq/L. He has diffuse crackles and wheezes, with marked accessory muscle use. Considering his acute hypercapnic and hypoxemic respiratory failure during a CF exacerbation, which is the MOST appropriate initial ventilatory management strategy?

A 28-year-old male with cystic fibrosis (CF) is in the ICU, intubated on assist-control ventilation for acute hypoxic respiratory failure. He has a central venous catheter and is on norepinephrine to maintain MAP >65 mmHg. He presented with 2 days of worsening cough, increased sputum, and fever. Vitals: T 39.5°C, HR 125 bpm, BP 88/50 mmHg (on norepinephrine 0.1 mcg/kg/min), RR 28 (ventilator set), SpO₂ 90% on FiO₂ 0.8. Labs: WBC 22,000/mm³ (85% neutrophils), lactate 4.8 mmol/L, creatinine 2.1 mg/dL (baseline 0.9), AST/ALT elevated. CXR: new bilateral infiltrates. Given his presentation and rapid deterioration, which of the following is the MOST appropriate immediate management for his life-threatening complication?

A 32-year-old man with cystic fibrosis (CF) is admitted to the ICU with a severe acute pulmonary exacerbation, requiring intubation and mechanical ventilation (assist-control mode) and vasopressor support (norepinephrine 0.1 µg/kg/min) for septic shock. He is febrile to 39.2 °C, heart rate 110 bpm, blood pressure 85/50 mmHg, respiratory rate 28 bpm, SpO₂ 92% on FiO₂ 0.8. Laboratory results: WBC 18,000/mm³, CRP 150 mg/L, lactate 4 mmol/L, creatinine 1.2 mg/dL (eGFR ~70 mL/min/1.73 m²). He has no known drug allergies, including beta-lactams. His prior sputum cultures grew Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus (MSSA). Which empiric antibiotic regimen is most appropriate to initiate?

A 28-year-old man with cystic fibrosis (weight 49 kg, height 1.70 m, BMI 17 kg/m²) is admitted to the ICU for a severe pulmonary exacerbation. He is mechanically ventilated and has required norepinephrine at 0.05 mcg/kg/min for the past 24 hours, with stable hemodynamics at this dose. Oral intake is nil. Which nutritional strategy is MOST appropriate to initiate in this patient?

A 25-year-old male with cystic fibrosis and pancreatic insufficiency is admitted to the ICU for a severe pulmonary exacerbation. He is kept NPO and on mechanical ventilation for several days. Nursing staff note new onset of easy bruising and prolonged bleeding from venipuncture sites. Which fat-soluble vitamin deficiency is most likely responsible for his bleeding tendency?

A 28-year-old man with cystic fibrosis (weight 70 kg) is admitted to the ICU with an acute pulmonary exacerbation requiring intubation and assist-control ventilation. He has a central venous catheter for norepinephrine support. Initial sputum cultures grew Pseudomonas aeruginosa (sensitive to tobramycin and meropenem) and MSSA. He was started on tobramycin 7 mg/kg (490 mg) IV once daily over 30 minutes and meropenem 2 g IV every 8 hours. On day 3, his oxygen saturation has improved from 88% to 94% on FiO₂ 40%, and WBC has decreased from 18,000 to 12,000/mm³. However, serum creatinine has risen from 0.8 mg/dL to 1.5 mg/dL (normal 0.6–1.2 mg/dL). A peak tobramycin level drawn 1 hour after infusion yesterday was 12 µg/mL (target peak 8–10 µg/mL). Which of the following is the MOST appropriate immediate action regarding his antibiotic regimen?

A 28-year-old man with cystic fibrosis is admitted to the ICU for a severe pulmonary exacerbation. He is on assist-control ventilation (100% FiO₂) and receiving norepinephrine 0.2 mcg/kg/min for septic shock. During evening rounds, the nurse reports the sudden onset of massive hemoptysis, with approximately 300 mL of bright red blood expectorated over 30 minutes. His blood pressure is 85/50 mm Hg, heart rate 125 bpm, and oxygen saturation has fallen from 94% to 88% on current ventilator settings. Which of the following is the most appropriate immediate management?