Infectious Diseases

A 67-year-old man is evaluated on hospital day 3. He was initially admitted for fever, chills, and left flank pain. His past medical history is significant for a T10 spinal cord injury resulting in neurogenic bladder, managed with intermittent clean catheterization. On presentation to the emergency department, his temperature was $39.1^\circ\text{C}$ ($102.4^\circ\text{F}$), blood pressure was $92/58\text{ mmHg}$, and heart rate was $114/\text{min}$. Laboratory testing demonstrated a leukocyte count of $16,500/\text{mm}^3$. He was aggressively resuscitated with intravenous fluids and empirically started on intravenous piperacillin-tazobactam and vancomycin for presumed urosepsis.

Today, the patient's temperature is $37.2^\circ\text{C}$ ($99.0^\circ\text{F}$), blood pressure is $122/78\text{ mmHg}$, and heart rate is $82/\text{min}$. He has been afebrile for the last 36 hours and is tolerating a normal oral diet. His flank pain has resolved. The urine culture collected on admission has finalized, growing $>10^5\text{ CFU/mL}$ of *Enterococcus faecalis*. Susceptibility testing results are as follows:

Blood cultures drawn on admission show no growth after 48 hours. Which of the following is the most appropriate next step in the patient's antimicrobial management?

A male patient, aged $58$, presents to the emergency department complaining of a $3$-day history of fever, chills, and severe left knee swelling. He has a past medical history significant for type $2$ diabetes mellitus but denies any recent falls or joint trauma. Initial vital signs reveal a temperature of $39.1^\circ\text{C}$ ($102.4^\circ\text{F}$), blood pressure of $110/70\text{ mm Hg}$, and heart rate of $112/\text{min}$. Physical examination highlights a warm, intensely erythematous, and exquisitely tender left knee with a noticeable effusion.

Arthrocentesis is performed, yielding frankly purulent synovial fluid with a leukocyte count of $85,000/\text{mm}^3$ ($90\%$ neutrophils). Blood and synovial fluid cultures are obtained, and he is empirically started on intravenous vancomycin and ceftriaxone before undergoing urgent arthroscopic lavage.

On hospital day $3$, the patient demonstrates clinical improvement and is currently afebrile. The microbiology laboratory reports that both the synovial fluid and blood cultures are growing *Staphylococcus aureus*. Susceptibility testing demonstrates that the isolate is resistant to penicillin but susceptible to oxacillin, cefazolin, and clindamycin. The patient's allergy profile notes a mild, non-pruritic maculopapular rash that occurred after taking amoxicillin during childhood; he has never experienced anaphylaxis, angioedema, or respiratory compromise associated with any medication.

Which of the following is the most appropriate antimicrobial regimen for this patient going forward?

A $31$-year-old male landscape architect seeks medical evaluation at a walk-in clinic in Rhode Island during mid-July. He describes a five-day history of low-grade fevers, profound fatigue, and a spreading skin lesion on his back. Yesterday, he began experiencing difficulty holding liquids in his mouth and noticed an inability to completely shut his right eye. Vital signs are temperature $37.8^\circ\text{C}$ ($100.0^\circ\text{F}$), blood pressure $122/78\text{ mmHg}$, pulse $74/\text{min}$, and respiratory rate $14/\text{min}$. Physical examination reveals a $12\text{ cm}$ annular, erythematous plaque with a distinct zone of central clearing on the right subscapular region. Neurologic examination demonstrates drooping of the right corner of the mouth, flattening of the right nasolabial fold, and an inability to close the right eyelid. Sensation to light touch on the face is intact. There is no nuchal rigidity, and the remainder of the examination is unremarkable. Which of the following is the most appropriate next step in management?

A 64-year-old man is evaluated in the intensive care unit for a persistent fever. He was admitted 8 days ago after a severe motor vehicle collision that resulted in multiple rib fractures, a pulmonary contusion, and a splenectomy. He has been mechanically ventilated since admission. Three days ago, he developed a temperature of 38.9°C (102.0°F), increased purulent endotracheal secretions, and increased oxygen requirements. A chest radiograph revealed a new right lower lobe consolidation. He was empirically started on intravenous cefepime, vancomycin, and amikacin. Today, his temperature is 37.4°C (99.3°F), and his oxygen requirements have decreased. The endotracheal aspirate culture from three days ago has grown Pseudomonas aeruginosa (>100,000 CFU/mL). Susceptibility testing shows the isolate is susceptible to cefepime, meropenem, piperacillin-tazobactam, and amikacin, but resistant to ciprofloxacin. No other organisms, including Staphylococcus aureus, have grown. Blood cultures obtained prior to antibiotic initiation are negative. Which of the following is the most appropriate next step in this patient's pharmacotherapy?

Match each clinical presentation of a newly diagnosed HIV patient with the most appropriate timing and rationale for initiating antiretroviral therapy (ART).

A 38-year-old woman is hospitalized for a 1-week history of severe lower back pain, generalized weakness, and recurrent chills. Her medical history is significant for intravenous drug use. Her temperature is $39.2^\circ C$ ($102.6^\circ F$), blood pressure is $112/68 \text{ mm Hg}$, and pulse is $115/\text{min}$. Physical examination reveals a new III/VI holosystolic murmur loudest at the cardiac apex. There is pronounced point tenderness over the lower lumbar spine, but no focal neurologic deficits are present. Laboratory studies show a leukocyte count of $15,200/\mu L$. Magnetic resonance imaging of the spine demonstrates abnormal signal intensity in the L4-L5 intervertebral disc and adjacent vertebral bodies, consistent with discitis and osteomyelitis. Blood cultures are drawn, and empiric therapy with intravenous vancomycin and cefepime is initiated. On hospital day 3, the patient's fever has improved. A transesophageal echocardiogram reveals a 1.4-cm vegetation on the mitral valve. Blood cultures are finalized and grow *Staphylococcus aureus* that is resistant to penicillin but susceptible to oxacillin, cefazolin, daptomycin, and vancomycin. Which of the following is the most appropriate next step in pharmacotherapy?

A 58-year-old woman is hospitalized for the treatment of infective endocarditis. She initially presented with a 3-week history of low-grade fever, fatigue, and a new heart murmur. Her history is notable for a dental extraction one month prior. Transesophageal echocardiography on admission revealed a 7-mm vegetation on the mitral valve leaflet. Three sets of blood cultures grew *Streptococcus sanguinis* with a penicillin minimum inhibitory concentration (MIC) of 0.05 mcg/mL. She was started on a planned 2-week synergistic regimen of intravenous aqueous penicillin G and intravenous gentamicin. On day 5 of hospitalization, the patient reports feeling clinically improved and has been afebrile for 48 hours. However, laboratory studies show her serum creatinine has increased from a baseline of 0.8 mg/dL to 2.1 mg/dL. Her urine output has mildly decreased over the past 24 hours. Which of the following is the most appropriate modification to her antimicrobial regimen?

A $65$-year-old man with a history of a renal transplantation presents to the emergency department with a $1$-day history of fever, severe headache, and confusion. His temperature is $39.2^\circ\text{C}$ ($102.6^\circ\text{F}$), blood pressure is $110/70\text{ mm Hg}$, and pulse is $115/\text{min}$. Physical examination reveals nuchal rigidity and bilateral papilledema. He is suspected of having acute bacterial meningitis. Arrange the following diagnostic and therapeutic steps in the most appropriate sequential order for managing this patient.

An $82$-year-old man is evaluated in the preadmission clinic prior to a scheduled elective right total knee arthroplasty. His past medical history is significant for hypertension, type $2$ diabetes mellitus, and benign prostatic hyperplasia. He reports feeling well and specifically denies dysuria, urinary frequency, urgency, gross hematuria, or flank pain. Vital signs are temperature $37.1^\circ\text{C}$ ($98.8^\circ\text{F}$), blood pressure $130/80\text{ mmHg}$, pulse $72\text{/min}$, and respirations $14\text{/min}$. Physical examination is unremarkable, with no costovertebral angle tenderness or suprapubic pain. A routine preoperative urinalysis reveals trace leukocyte esterase, positive nitrites, and $15$-$20$ white blood cells per high-power field. Which of the following is the most appropriate next step in management regarding this patient's urinary findings?

A 62-year-old man is admitted to the hospital with a 3-week history of low-grade fevers, fatigue, and progressive shortness of breath. His medical history is significant for mitral valve prolapse with severe regurgitation. Temperature is $38.4^{\circ}\text{C}$ ($101.1^{\circ}\text{F}$), pulse is $102/\text{min}$, and blood pressure is $110/65 \text{ mmHg}$. Cardiac examination reveals a grade 3/6 holosystolic murmur at the apex. Small, painless, erythematous macules are noted on the palms.

Laboratory studies show:
- Leukocyte count: $14,200/\text{mm}^3$
- Hemoglobin: $10.4 \text{ g/dL}$
- Serum creatinine: $2.6 \text{ mg/dL}$ (baseline $0.9 \text{ mg/dL}$ three months ago)

Urinalysis reveals 2+ protein, 15-20 red blood cells/hpf, and the presence of red blood cell casts.

Three sets of blood cultures are drawn, and empiric intravenous vancomycin and cefepime are initiated. Transesophageal echocardiography reveals a $1.4\text{-cm}$ oscillating vegetation on the posterior mitral leaflet.

On hospital day 3, all blood culture bottles grow *Enterococcus faecalis*. Antimicrobial susceptibility testing reveals the following minimum inhibitory concentrations (MIC):
- Ampicillin: $\leq 1 \ \mu\text{g/mL}$ (Susceptible)
- Vancomycin: $1 \ \mu\text{g/mL}$ (Susceptible)
- Gentamicin (high-level testing): Susceptible

The laboratory report includes a standard comment: 'Enterococci are intrinsically resistant to cephalosporins, antistaphylococcal penicillins, and clindamycin in vitro.'

The patient's serum creatinine remains elevated at $2.7 \text{ mg/dL}$.

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

A 68-year-old man is brought to the emergency department by his son because he has been acting confused since yesterday morning. For the past three days, he has also experienced subjective fevers, chills, and a cough productive of yellowish sputum. His medical history includes hypertension, benign prostatic hyperplasia, and osteoarthritis. He does not use tobacco, alcohol, or illicit substances. His temperature is $38.7^\circ\text{C}$ ($101.7^\circ\text{F}$), pulse is $102/\text{min}$, blood pressure is $115/70\text{ mmHg}$, and respiratory rate is $24/\text{min}$. Pulse oximetry indicates an oxygen saturation of $92\%$ on room air. He appears acutely ill and is oriented only to person. Pulmonary auscultation reveals crackles and bronchial breath sounds over the left lower lung fields. Laboratory evaluation is notable for a leukocyte count of $15,500/\text{mm}^3$ and a blood urea nitrogen (BUN) level of $24\text{ mg/dL}$. Chest radiography demonstrates a dense left lower lobe consolidation. The patient is admitted to the general medical ward. Which of the following is the most appropriate empiric pharmacotherapy for this patient?

During morning rounds on the medical ward, a consulting physician evaluates a patient admitted overnight for persistent fever, generalized weakness, and dark urine. The patient was seen at an urgent care center one week ago for an erythematous, expanding annular rash with central clearing on the right thigh following a camping trip in Massachusetts. Oral doxycycline was initiated at that time. Although the rash has faded, the patient reports worsening systemic symptoms. Current vital signs include a temperature of $39.2^\circ\text{C}$ ($102.6^\circ\text{F}$), blood pressure of $110/70 \text{ mmHg}$, and a heart rate of $112/\text{min}$. Physical examination is notable for scleral icterus and mild splenomegaly. Laboratory findings show a hemoglobin level of $7.8 \text{ g/dL}$, platelet count of $95,000/\text{mm}^3$, elevated indirect bilirubin, and significantly elevated lactate dehydrogenase. A peripheral blood smear reveals pleomorphic intraerythrocytic organisms, with occasional tetrad formations. Which of the following is the most appropriate modification to this patient's antimicrobial regimen?

A 35-year-old man comes to the clinic for a routine 6-month sexually transmitted infection screening. He is currently asymptomatic and has no somatic complaints. He reports having multiple male sexual partners. He has no known drug allergies and takes a daily tenofovir-emtricitabine regimen for HIV pre-exposure prophylaxis.

His medical history is significant for a diagnosis of primary syphilis $2$ years ago, which was appropriately treated with a single intramuscular injection of benzathine penicillin G. At the time of that diagnosis, his Rapid Plasma Reagin (RPR) titer was $1:64$. Six months after his treatment, the titer had decreased to $1:2$.

Review of his medical records shows that during his last routine screening $6$ months ago, his RPR titer remained stable at $1:2$.

Today, his physical examination is unremarkable, with no evidence of chancre, mucosal lesions, maculopapular rash, or neurological abnormalities.

Laboratory results from today's visit:
HIV antigen/antibody test: Negative
RPR: Positive, titer $1:32$
*Treponema pallidum* particle agglutination (TP-PA): Positive

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

Match each patient's clinical presentation with the most appropriate antimicrobial stewardship-guided management step.

A 42-year-old man presents to the emergency department with a 4-week history of productive cough, low-grade fever, drenching night sweats, and a 5-kg (11-lb) weight loss. He emigrated from a country with a high incidence of tuberculosis two years ago. Vital signs show a temperature of 38.1°C (100.6°F), heart rate of 92/min, blood pressure of 120/78 mm Hg, respiratory rate of 18/min, and oxygen saturation of 97% on room air. Physical examination reveals bronchial breath sounds and crackles in the right upper lung field. He is currently waiting in the general triage area. Arrange the following management steps in the most appropriate chronological order.

Match each clinical presentation of genital ulcer disease to the most appropriate first-line pharmacotherapy.

An 82-year-old woman residing in a skilled nursing facility is evaluated during a routine monthly check-up. Her medical history includes Alzheimer dementia, hypertension, and type 2 diabetes mellitus. The facility staff requested a urinalysis today because they noted her urine has appeared cloudy and malodorous over the past three days. The patient has no complaints and denies any pain. Temperature is 37.0°C (98.6°F), blood pressure is 138/82 mm Hg, pulse is 76/min, and respirations are 14/min. The patient is alert, pleasant, and oriented to her own name, which is consistent with her baseline mental status. Abdominal examination reveals a soft, non-distended abdomen with no suprapubic or costovertebral angle tenderness. A clean-catch urinalysis shows a specific gravity of 1.015, pH 6.5, positive leukocyte esterase, positive nitrites, and 45 white blood cells/hpf. Which of the following is the most appropriate next step in management?

A 52-year-old man is brought to the emergency department by his wife due to a 24-hour history of high fever, severe generalized headache, and progressive confusion. On physical examination, his temperature is 39.2°C (102.6°F), blood pressure is 110/70 mmHg, heart rate is 115/min, and respiratory rate is 18/min. He is lethargic but arousable. Neurologic examination reveals marked nuchal rigidity and a new, mild right-sided hemiparesis. Fundoscopic examination shows early papilledema. The physician suspects acute bacterial meningitis. Arrange the following steps in the most appropriate chronological order for the initial management of this patient.

A $68$-year-old man is evaluated in the intensive care unit for a new-onset fever and increased respiratory secretions. He has been receiving mechanical ventilation for $7$ days following a severe cerebrovascular accident. His temperature is $38.8^\circ\text{C}$ ($101.8^\circ\text{F}$), blood pressure is $110/70\text{ mmHg}$, and pulse is $105/\text{min}$. Physical examination reveals coarse crackles in the right lower lung field. A chest radiograph demonstrates a new right lower lobe infiltrate. Endotracheal aspiration is performed, and empiric intravenous therapy with cefepime, tobramycin, and vancomycin is initiated.

Forty-eight hours later, the patient's temperature is $37.2^\circ\text{C}$ ($99.0^\circ\text{F}$) and his oxygenation has steadily improved. The endotracheal aspirate culture grows $10^6\text{ CFU/mL}$ of *Pseudomonas aeruginosa*. Antimicrobial susceptibility testing indicates the organism is susceptible to cefepime, meropenem, and tobramycin, but resistant to levofloxacin. No other organisms are isolated. Which of the following is the most appropriate next step in the management of this patient's pharmacotherapy?

A 68-year-old male is currently receiving care in the intensive care unit for acute respiratory distress syndrome secondary to severe acute pancreatitis. He has been mechanically ventilated for the past 11 days. Over the last 48 hours, his oxygen requirements have increased, and he has developed copious purulent endotracheal secretions. His temperature is 38.8°C (101.8°F), blood pressure is 110/65 mm Hg, and pulse is 112/min. Physical examination reveals coarse crackles in the right lung base. A portable chest radiograph demonstrates a new right lower lobe consolidation. Endotracheal aspirate and blood cultures are obtained, and the patient is empirically started on intravenous vancomycin, meropenem, and tobramycin.

Two days later, the patient's clinical status has improved, and he is afebrile. Blood cultures show no growth. The endotracheal aspirate culture yields heavy growth of *Enterobacter cloacae*. The antimicrobial susceptibility report is as follows:

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