Infectious Diseases

An intensivist is reviewing the microbiological data for a 48-year-old male patient on mechanical ventilation. The patient was admitted to the intensive care unit 8 days ago following a motor vehicle collision that resulted in severe head trauma. Three days ago, he developed a new fever of $39.2^\circ\text{C}$ ($102.6^\circ\text{F}$), thick endotracheal secretions, and worsening hypoxemia. A chest radiograph at that time revealed a new left lower lobe consolidation. He was empirically started on intravenous vancomycin, cefepime, and tobramycin for suspected ventilator-associated pneumonia (VAP).

Today, the patient is clinically improved. His temperature is $37.4^\circ\text{C}$ ($99.3^\circ\text{F}$), and his oxygen requirements have decreased. The endotracheal aspirate culture obtained prior to antibiotic initiation now shows:

- Heavy growth of *Pseudomonas aeruginosa*
- Moderate growth of *Candida albicans*
- No *Staphylococcus aureus* isolated

Antimicrobial susceptibility testing for the *Pseudomonas aeruginosa* isolate demonstrates susceptibility to cefepime, meropenem, piperacillin-tazobactam, and tobramycin. Blood cultures drawn at the time of the fever have remained sterile.

Which of the following is the most appropriate next step in the pharmacologic management of this patient?

An intensive care unit team is conducting morning rounds. The patient is a 68-year-old female who was admitted one week ago following an out-of-hospital cardiac arrest. She was successfully resuscitated and placed on mechanical ventilation. Three days ago, her condition became complicated with a new fever of 39.2°C (102.6°F), worsening hypoxemia, and purulent endotracheal secretions. A chest radiograph demonstrated a new right lower lobe consolidation. Empiric intravenous vancomycin and cefepime were initiated for a presumed ventilator-associated pneumonia.

Today, she exhibits significant clinical improvement. She is afebrile with a temperature of 37.1°C (98.8°F), blood pressure of 128/78 mm Hg, and heart rate of 82/min. Her ventilator settings have been successfully weaned. An endotracheal aspirate culture obtained at the onset of fever demonstrates heavy growth of Pseudomonas aeruginosa. Susceptibility testing shows the organism is susceptible to cefepime, piperacillin-tazobactam, and meropenem, but resistant to levofloxacin. No other organisms are isolated. A nasal swab polymerase chain reaction (PCR) screen for methicillin-resistant Staphylococcus aureus (MRSA) obtained three days ago is negative.

Based on the culture and susceptibility results, which of the following is the most appropriate next step in the pharmacologic management of this patient?

A 29-year-old female graduate student presents to the university health clinic complaining of burning with urination and increased urinary frequency for the past $48$ hours. She denies any back pain, nausea, vomiting, or vaginal discharge. Her temperature is $37.0^\circ\text{C}$ ($98.6^\circ\text{F}$), blood pressure is $110/70\text{ mm Hg}$, and pulse is $78\text{/min}$. Physical examination demonstrates mild suprapubic discomfort on deep palpation but no costovertebral angle tenderness. A urine sample collected at an outside urgent care facility three days ago has just returned positive for *Klebsiella pneumoniae*. The microbiology report flags the isolate as an extended-spectrum beta-lactamase (ESBL) producer. Susceptibility testing reveals resistance to ceftriaxone, cefepime, and ciprofloxacin, but confirms susceptibility to nitrofurantoin, fosfomycin, and meropenem. Which of the following is the most appropriate next step in management?

Correlate the following clinical presentations of central nervous system and disseminated infections in immunocompromised hosts with their most appropriate primary targeted management.

A 35-year-old man with untreated HIV infection is brought to the emergency department by his partner due to a 2-week history of progressively worsening headache, fever, and confusion. His temperature is 38.6°C (101.5°F), blood pressure is 120/78 mmHg, and heart rate is 102/min. Physical examination reveals nuchal rigidity and bilateral sixth cranial nerve palsies. Laboratory studies show a CD4 cell count of 28/mm³. A lumbar puncture is performed, and cerebrospinal fluid (CSF) analysis reveals a leukocyte count of 350/mm³ (85% lymphocytes), glucose of 30 mg/dL, and protein of 150 mg/dL. CSF acid-fast bacilli smear is positive. The patient is admitted to the intensive care unit and started on isoniazid, rifampin, pyrazinamide, ethambutol, and intravenous dexamethasone. Which of the following is the most appropriate timing for initiating antiretroviral therapy in this patient?

A 54-year-old woman is evaluated in the oncology ward for a new-onset fever. She is currently on day 10 of induction chemotherapy for acute myeloid leukemia. Her temperature is 38.8°C (101.8°F), blood pressure is 105/65 mmHg, and heart rate is 112/min. Laboratory analysis shows a white blood cell count of 400/mm³ with an absolute neutrophil count (ANC) of 150/mm³. She has a central venous port in her right internal jugular vein.

Arrange the following interventions in the most appropriate chronological sequence for managing this patient's condition.

A 72-year-old man is evaluated in the hospital on day 3 of admission for community-acquired pneumonia. He initially presented to the emergency department with a 2-day history of fever, productive cough, and shortness of breath. His medical history is significant for hypertension and mild chronic obstructive pulmonary disease. On admission, his temperature was $38.9^\circ\text{C}$ ($102^\circ\text{F}$), blood pressure was $118/76\text{ mmHg}$, pulse was $102/\text{min}$, and respiratory rate was $22/\text{min}$. Oxygen saturation was $92\%$ on room air. Chest radiography revealed a right lower lobe consolidation. He was empirically started on intravenous ceftriaxone and intravenous azithromycin. Today, the patient is afebrile, his pulse is $82/\text{min}$, and his respiratory rate is $16/\text{min}$. He is resting comfortably and eating a regular diet. Blood cultures drawn on admission are now growing *Streptococcus pneumoniae*. Susceptibility testing shows the organism is highly susceptible to penicillin, amoxicillin, ceftriaxone, and levofloxacin, but resistant to azithromycin. Which of the following is the most appropriate next step in antibiotic management?

A 54-year-old man presents to the clinic with a 5-day history of fever, severe fatigue, drenching sweats, and dark urine. He recently returned from a 2-week camping trip in Nantucket, Massachusetts. Two days ago, he was evaluated at an urgent care center where a 6-cm expanding erythematous plaque with central clearing was noted on his right thigh. He was prescribed oral doxycycline for presumed early localized Lyme disease. Despite compliance with the medication, his fever and fatigue have persisted and worsened. His temperature is 38.9°C (102.0°F), blood pressure is 116/74 mm Hg, and pulse is 108/min. Physical examination reveals pale conjunctivae, mild scleral icterus, and a fading erythematous patch on the right thigh. There is no respiratory distress. Laboratory studies show:

Hemoglobin: 9.2 g/dL
Platelets: 88,000/mm³
Leukocytes: 4,500/mm³
Total bilirubin: 3.4 mg/dL
Indirect bilirubin: 2.8 mg/dL
Lactate dehydrogenase: 650 U/L

A peripheral blood smear demonstrates pleomorphic intraerythrocytic ring forms and occasional tetrads. Which of the following is the most appropriate pharmacotherapy for this patient's current condition?

A 68-year-old man is admitted to the hospital due to a 3-week history of low-grade fevers, progressive fatigue, and dyspnea on exertion. He has a history of hypertension and osteoarthritis. His temperature is 38.2°C (100.8°F), blood pressure is 128/76 mm Hg, pulse is 92/min, and respirations are 16/min. Physical examination reveals a new grade 3/6 holosystolic murmur best heard at the cardiac apex and radiating to the axilla. Splinter hemorrhages are noted on the fingernails. Transesophageal echocardiography demonstrates a 1.2-cm mobile vegetation on the anterior leaflet of the mitral valve with moderate mitral regurgitation. Three sets of blood cultures are obtained, and the patient is started on empiric intravenous vancomycin and cefepime. Forty-eight hours later, all three blood cultures grow *Enterococcus faecalis*. Antimicrobial susceptibility testing results are as follows:

Which of the following is the most appropriate definitive pharmacotherapy for this patient?

Match each of the following high-risk infectious exposure scenarios with the most appropriate immediate management or post-exposure prophylaxis (PEP) step.

Emergency medical services bring a 61-year-old man to the emergency department after his family found him confused and febrile. His wife reports that he complained of a severe, throbbing headache yesterday before becoming progressively somnolent this morning. His past medical history includes hypertension and type 2 diabetes mellitus. Temperature is $39.4^{\circ}\text{C}$ ($102.9^{\circ}\text{F}$), blood pressure is $138/86\text{ mmHg}$, pulse is $112/\text{min}$, and respirations are $18/\text{min}$. On physical examination, the patient is lethargic and oriented only to person. He strongly resists passive neck flexion. Fundoscopic examination reveals bilateral blurring of the optic disc margins. Neurologic examination demonstrates a left-sided facial droop and decreased strength in the left upper extremity compared to the right. Arrange the following steps in the most appropriate chronological order for managing this patient.

A 42-year-old man is evaluated in the hospital for ongoing management of right knee septic arthritis. He originally presented 3 days ago with an acutely painful, swollen right knee and a temperature of 38.8°C (101.8°F). Initial arthrocentesis revealed purulent synovial fluid with 95,000 leukocytes/mm³, and a Gram stain demonstrated Gram-positive cocci in clusters. He underwent prompt arthroscopic irrigation and debridement, and was empirically started on intravenous vancomycin. Today, the patient reports feeling much better, his knee pain has decreased, and he has been afebrile for 24 hours. Final synovial fluid cultures are positive for Staphylococcus aureus. Antimicrobial susceptibility testing shows that the isolate is resistant to penicillin but susceptible to oxacillin, cefazolin, clindamycin, and vancomycin. Which of the following is the most appropriate next step in the antibiotic management of this patient?

During a preoperative assessment, a 74-year-old male is reviewed by the surgical team three days before an elective left total hip arthroplasty. He has longstanding osteoarthritis, diet-controlled type 2 diabetes mellitus, and mild benign prostatic hyperplasia. The patient feels well and explicitly denies any current urinary urgency, dysuria, increased frequency, or flank discomfort. His temperature is 37.0°C (98.6°F), blood pressure is 132/84 mmHg, and heart rate is 76/min. Aside from left hip stiffness and an antalgic gait, the physical examination is unremarkable.

Laboratory investigations are obtained as part of standard preoperative protocols. A midstream urine sample shows 18 leukocytes/hpf, positive leukocyte esterase, and negative nitrites. A reflex urine culture subsequently isolates $>10^5$ CFU/mL of Extended-Spectrum Beta-Lactamase (ESBL)-producing *Escherichia coli*. The isolate is resistant to ceftriaxone, ciprofloxacin, and trimethoprim-sulfamethoxazole, but retains susceptibility to meropenem, nitrofurantoin, and fosfomycin.

Based on these findings, which of the following is the most appropriate next step in the management of this patient's urinary findings?

Match each clinical presentation of infective endocarditis with the most appropriate empiric or targeted antimicrobial regimen.

A 68-year-old man is evaluated in the intensive care unit for worsening oxygenation and a new-onset fever. He was admitted 8 days ago for severe acute respiratory distress syndrome secondary to influenza A, requiring endotracheal intubation and mechanical ventilation. Over the past 48 hours, his fraction of inspired oxygen (FiO2) requirement has increased from 40% to 60%. His temperature is 39.1°C (102.4°F), blood pressure is 110/65 mm Hg, and pulse is 108/min. Physical examination reveals coarse rhonchi bilaterally and copious, purulent secretions from the endotracheal tube. A chest radiograph demonstrates a new consolidation in the left lower lobe. Endotracheal aspirate and blood cultures are obtained. The patient is empirically started on intravenous piperacillin-tazobactam, vancomycin, and amikacin. Three days later, his clinical condition has significantly improved, and his oxygen requirements have decreased. The endotracheal aspirate culture yields heavy growth of Pseudomonas aeruginosa. Susceptibility testing indicates the isolate is sensitive to piperacillin-tazobactam, ceftazidime, cefepime, and ciprofloxacin, but resistant to amikacin. Blood cultures show no growth after 72 hours. Which of the following is the most appropriate next step in pharmacotherapy?

A 42-year-old woman with acute myeloid leukemia presents to the emergency department with a fever. She received her last cycle of induction chemotherapy 12 days ago. She reports no cough, dyspnea, abdominal pain, or dysuria. Her temperature is 38.8°C (101.8°F), blood pressure is 118/76 mm Hg, pulse is 98/min, and respirations are 16/min. Physical examination reveals a right internal jugular totally implantable venous access port with no overlying erythema, induration, or tenderness. The lungs are clear to auscultation. There are no oral ulcers or skin rashes. Laboratory studies show:

Hemoglobin: 9.2 g/dL
Leukocyte count: 400/mm³
Absolute neutrophil count: 120/mm³
Platelet count: 45,000/mm³

Blood and urine cultures have been obtained. Which of the following is the most appropriate next step in pharmacotherapy?

A 65-year-old man is brought to the emergency department by his family due to a severe headache, fever, and progressive confusion over the past 12 hours. His temperature is 39.2°C (102.6°F), blood pressure is 110/70 mmHg, pulse is 112/min, and respiratory rate is 18/min. On examination, the patient is lethargic and oriented only to person. Neck flexion produces involuntary hip and knee flexion. Fundoscopic examination reveals blurring of the optic disc margins bilaterally. He has a medical history of type 2 diabetes mellitus and hypertension.

Arrange the following next steps in the management of this patient in the most appropriate chronological order.

A 28-year-old woman is evaluated in the hospital on the third day of admission for acute pyelonephritis. On admission, she presented with fever, chills, right-sided flank pain, and dysuria. She was started on empiric intravenous ceftriaxone. Today, she reports feeling much better and has been afebrile for the past 24 hours. Her right costovertebral angle tenderness has largely resolved. She is tolerating a regular diet.

Urine culture obtained on admission has grown >$10^5$ CFU/mL of *Klebsiella pneumoniae*. Antimicrobial susceptibility testing results are as follows:

Which of the following is the most appropriate next step in management?

A 54-year-old man is evaluated in the hospital on hospital day 3 for ongoing management of a severe skin and soft tissue infection of the right lower extremity. He initially presented with high fever, chills, and a rapidly expanding area of erythema and induration. Blood cultures drawn on admission have now returned positive for methicillin-susceptible Staphylococcus aureus (MSSA). His empiric antimicrobial regimen since admission has consisted of intravenous vancomycin and cefepime. The patient's medical record indicates an allergy to penicillin, which he describes as a flat, red rash on his chest that occurred 20 years ago when taking amoxicillin. He explicitly denies any history of facial swelling, hives, or breathing difficulties. He is currently hemodynamically stable, his temperature is 37.4°C (99.3°F), and the erythema has significantly receded. Subsequent blood cultures drawn 48 hours after admission show no growth to date.

Which of the following is the most appropriate pharmacologic intervention at this time?

An 82-year-old woman is brought to the emergency department from a skilled nursing facility due to a 2-day history of worsening confusion and agitation. She has a medical history of moderate Alzheimer dementia, type 2 diabetes mellitus, hypertension, and urge urinary incontinence. Two weeks ago, she was evaluated for worsening incontinence, and oral oxybutynin was added to her regimen. She cannot provide a reliable history, but the facility staff reports no observed coughing, vomiting, diarrhea, or signs of pain during urination. The staff did note that her urine has been cloudy and malodorous for the past 3 days.

Vital signs are temperature $37.0^\circ\text{C}$ ($98.6^\circ\text{F}$), blood pressure $138/84\text{ mmHg}$, pulse $88/\text{min}$, and respiratory rate $16/\text{min}$. Oxygen saturation is $98\%$ on room air. The patient is disoriented to time and place and frequently picks at her clothing. The abdomen is soft, non-tender, and without suprapubic distension. Bilateral costovertebral angle percussion elicits no reaction.

Laboratory evaluation shows a leukocyte count of $8,500/\text{mm}^3$, serum sodium of $138\text{ mEq/L}$, serum creatinine of $1.0\text{ mg/dL}$, and blood glucose of $115\text{ mg/dL}$. Urinalysis obtained via straight catheterization reveals:

Color: Yellow, cloudy
Specific gravity: $1.018$
Leukocyte esterase: Positive
Nitrites: Positive
WBCs: $30\text{-}40/\text{hpf}$
RBCs: $0\text{-}2/\text{hpf}$
Bacteria: Many

A urine culture is sent to the laboratory. Which of the following is the most appropriate next step in management?