The following cases and commentary, which address pneumonia, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 14).
Case 1: Fever and dyspnea in leukemia patient
A 45-year-old woman is hospitalized in December because of a one-day history of dyspnea, fever, pleuritic chest pain, and a nonproductive cough. The patient has acute myeloid leukemia and has undergone induction chemotherapy with resultant prolonged granulocytopenia. She has been hospitalized several times in a building that has several large construction projects in progress. Her last admission was seven days ago. The patient has worn a mask when in the hospital. Her son has a mild upper respiratory tract infection; other family members are well. All family members received influenza vaccine.
On physical examination on admission, temperature is 39°C (102.2°F), pulse rate is 112/min, respiration rate is 24/min, and blood pressure is 118/62 mm/Hg. Fine crackles are heard. There are no skin lesions. The leukocyte count is 1000/µL (1.0× 109/L) with 50% neutrophils, and routine blood chemistry studies are normal. A chest radiograph shows a wedge-shaped infiltrate in the left lower lobe. A CT scan shows that the opacity appears to have a “halo sign.”
Which of the following pathogens is most likely causing this patient's acute findings?
A. Legionella pneumophila
B. Varicella virus
C. Candida albicans
D. Influenza A virus
E. Aspergillus fumigatus
Case 2: Recent antibiotic use
A 79-year-old woman is hospitalized for treatment of community-acquired pneumonia. The patient is frail but is able to live at home. Two months ago, she had a urinary tract infection that was treated with ciprofloxacin. She had an apparent upper respiratory tract infection seven days ago and developed left-sided pleuritic chest pain and shaking chills one day before admission.
On physical examination, temperature is 38.7°C (101.7°F), pulse rate is 110/min and regular, respiration rate is 24/min, and blood pressure is 90/60 mm/Hg. Examination of the chest discloses crackles, diminished breath sounds at the left lung base, and egophony. The leukocyte count is 31,000/µL (31 × 109/L) with 85% segmented neutrophils and 7% band forms. The patient is unable to produce sputum for examination. A chest radiograph shows a left lower lobe pulmonary infiltrate.
According to the hospital's antibiogram, local isolates of Streptococcus pneumoniae are often multi-resistant (i.e., 30% of isolates are resistant to penicillin, of which two thirds of these are high-grade resistance) and a comparable number are resistant to macrolides.
Which of the following is the most appropriate therapy for this patient at this time?
A. Intravenous vancomycin plus ceftriaxone
B. Intravenous ceftriaxone plus azithromycin
C. Intravenous levofloxacin
D. Oral telithromycin
Case 3: IV antibiotics during pneumonia recovery
A 72-year-old male smoker with chronic obstructive pulmonary disease was hospitalized two days ago because of patchy left lower lobe pneumonia accompanied by fever, cough, and dyspnea. His initial leukocyte count was 14,300/µL (14.3 × 109/L). Intravenous levofloxacin and supplemental oxygen, 2 L/min by nasal prongs, were started on admission.
On hospital day three, the patient has been afebrile for the past 18 hours. He has good oral intake, his cough has decreased, and he is no longer dyspneic. Arterial oxygen saturation is 92% by pulse oximetry with the patient breathing room air, and his leukocyte count is now 9600/µL (9.6 × 109/L). A repeat chest radiograph shows no change in the size of the left lower lobe infiltrate.
Which of the following is most appropriate at this time?
A. CT scan of the chest
B. Consultation for fiberoptic bronchoscopy
C. Replacement of intravenous levofloxacin with oral levofloxacin
D. Addition of intravenous ceftriaxone
Case 4: Pneumonia with bioterrorism threat
A 27-year-old man comes to the emergency department of a hospital in New Mexico because of dyspnea, fever, malaise, nausea, vomiting and increased watery sputum that began last night. Hemoptysis developed this morning. The patient works as a veterinarian at the local aquarium. Medical history is unremarkable, and he takes no medications. His mother, with whom he lives, died of pneumonia four days ago. The United States has been on a Code Red advisory alert (high threat) for the past ten days.
On physical examination, the patient appears acutely ill. Temperature is 39.8°C (103.6°F), pulse rate is 118/min, respiration rate is 32/min, and blood pressure is 92/48 mm/Hg. There is no lymphadenopathy. Chest examination discloses tachycardia, dullness to percussion throughout the entire right lung field, and egophony at the level of the right mid-scapula on auscultation. Abdominal examination is normal. A chest radiograph shows an infiltrate in the right lower lobe and the inferior portions of the right upper lobe.
After blood cultures are obtained, ceftriaxone and erythromycin are started, but the patient does not improve. Blood cultures are later reported to be growing an as-yet-unidentified gram-negative rod.
Which of the following pathogens is most likely causing this patient's disorder?
A. Bacillus anthracis
B. Coxiella burnetii
C. Haemophilus influenzae
D. Francisella tularensis
E. Yersinia pestis
Case 5: Pneumonia progressed to renal failure
A previously healthy 32-year-old woman is hospitalized for community-acquired pneumonia and suspected empyema. Her temperature is 38.9°C (102.0°F) and her blood pressure is 115/72 mm/Hg. Laboratory studies show an elevated leukocyte count, decreased platelet count, blood urea nitrogen of 30 mg/dL (10.71 mmol/L), and serum creatinine of 2.4 mg/dL (212.21 µmol/L). The pleural space is drained via thoracotomy tube. Hypotension develops and does not resolve with fluid administration; vasopressor support is started. She now has anuric acute renal failure. Leukocyte count remains elevated, blood urea nitrogen is 110 mg/dL (39.28 mmol/L), serum potassium is 5.9 mEq/L (5.9 mmol/L) (despite sodium polystyrene sulfonate), and serum bicarbonate is 15 mEq/L (15 mmol/L). Arterial blood pH is 7.24.
Which of the following is the best approach to management for this patient?
A. Alternate-day hemodialysis
B. Daily hemodialysis
C. Intravenous furosemide
D. Intravenous bicarbonate infusion
E. Fenoldopam infusion
Case 6: Lower lobe pneumonia after antibiotic use
A 44-year-old woman is hospitalized from the emergency department because of left lower lobe pneumonia. Medical history is unremarkable except for recurrent urinary tract infections for which she has received various antibiotics.
Temperature on admission is 39.2°C (102.5°F), and intravenous levofloxacin is begun. One day later, her temperature has decreased to 38.1°C (100.5°F), and blood cultures obtained in the emergency department are growing Streptococcus pneumoniae with an minimal inhibitory concentration (MIC) for penicillin equal to 1 µg/mL (intermediate-level resistance).
Which of the following is the most appropriate therapy at this time?
A. Change to cefuroxime
B. Change to vancomycin
C. Change to ampicillin–sulbactam
D. Change to linezolid
E. Continue levofloxacin
Case 7: Shortness of breath
A 52-year-old woman has a 2-month history of shortness of breath and a 1-month history of a nonproductive cough. Both symptoms are increasing. The patient has no allergies or exposures to occupational or environmental pulmonary contaminants. Medical history is unremarkable, and her only medication is an H2-receptor antagonist.
On physical examination, she appears dyspneic. Examination is otherwise normal except for a large healing bruise on her thigh that developed when she slipped in a hot tub.
A chest radiograph is normal. Pulmonary function tests show moderate obstructive disease with a slightly low diffusing capacity for carbon monoxide (DLCO). A sputum culture is positive for mycobacteria.
Which of the following most likely explains this patient's positive sputum culture?
A. Mycobacterium avium complex hypersensitivity pneumonitis
B. Tuberculous pneumonia
C. Nocardia pneumonia
D. Rhodococcus pneumonia
E. A contaminant in the sputum culture
Case 8: Altered mental status after pneumonia
An 88-year-old man is hospitalized for pneumonia and poor nutritional intake. On physical examination, he is coughing. The temperature is 37.8°C (100°F), pulse rate is 90/min, and respiration rate is 16/min. Chest examination reveals crackles in the left lower lobe, and the chest radiograph confirms the diagnosis of pneumonia. Antibiotic therapy is begun, and the patient's cough resolves within 3 days and the vital signs return to normal.
On hospital day 4, the patient becomes inattentive, confused, and drowsy, with apparent hallucinations and fluctuating mental status. His vital signs remain normal, and other than his mental status, his physical examination is normal.
Which of the following is the most likely cause of this patient's change in mental status?
A. Alcohol abstinence syndrome
B. Drug reaction
Answers and Commentary
Correct answer: E. Aspergillus fumigatus.
Immunosuppressed patients are at increased risk of developing nosocomial pneumonia, even when mechanical ventilation is not required. The pneumonia is most often caused by inhalation of aerosols or droplets contaminated with Legionella species, Aspergillus species, respiratory syncytial virus, or influenza virus. The clinical presentation includes fever, headache, myalgias, diarrhea and cough. Respiratory insufficiency, sepsis and multi-system organ failure may develop and may lead to death. Initial findings in patients with these infections tend to be similar. However, this patient most likely has an Aspergillus infection because only this organism causes a “halo sign” (a nodular lesion with a surrounding ground-glass appearance) on chest radiographs. Her pleuritic chest pain and fever also support this diagnosis. Aspergillus fumigatus infection occurs most often, but infections due to A. flavus and A. terrus have also been reported.
Legionella pneumophila is also associated with construction and cannot be ruled out completely at this time. However, L. pneumophila pneumonia tends to occur in clusters, is associated with warmer weather, most often causes a lobar pneumonia and gastrointestinal symptoms, and would not induce a halo sign. Varicella (chickenpox) presents with a vesicular rash in various stages of development, and this patient does not have any skin lesions. Candida species rarely cause pneumonia. Influenza A virus causes both upper and lower respiratory tract disease that can be serious in immunosuppressed patients. However, this patient has no epidemiologic risk factors for influenza, and this virus would not cause her radiographic findings.
- Immunosuppressed patients are at increased risk for developing nosocomial pneumonia even when mechanical ventilation is not required.
- A “halo sign” (a nodular lesion with a surrounding ground-glass appearance) on chest radiographs is characteristic of Aspergillus pneumonia.
Correct answer: B. Intravenous ceftriaxone plus azithromycin.
Most experts and guidelines support the use of a third-generation cephalosporin plus a macrolide (which is directed against atypical pathogens) for treatment of community-acquired pneumonia. Administration of intravenous ceftriaxone and azithromycin is therefore the most appropriate of the regimens listed.
Pneumococcal strains are becoming increasingly resistant to penicillins and macrolides. For example, β-lactam resistance predicts treatment failure in patients with meningitis because of limited central nervous system penetration, and vancomycin and ceftriaxone are therefore used to treat pneumococcal meningitis until minimal inhibitory concentrations (MICs) are available. However this patient has pneumococcal pneumonia, and there are no compelling data linking MICs and outcome after β-lactam therapy for pneumococcal pneumonia.
Fluoroquinolones should not be used as first-line therapy for community-acquired pneumonia in order to limit the massive increase in fluoroquinolone resistance in bowel flora. This patient's previous use of ciprofloxacin also predisposes her to having a fluoroquinolone-resistant pneumococcal strain. Telithromycin is active in vitro against organisms that are resistant to macrolides. However, even fewer data are available correlating MICs and outcome when macrolides are used for treatment of community-acquired pneumonia. In addition, telithromycin is approved only for mild-to-moderate community-acquired pneumonia and is not available parenterally. Finally, a recent study has also reported that three otherwise healthy patients who took telithromycin developed acute hepatotoxicity.
- Pneumococcal strains are becoming increasingly resistant to penicillins and macrolides.
- Most experts and guidelines support the use of a third-generation cephalosporin plus a macrolide for treatment of community-acquired pneumonia.
Correct answer: C. Replacement of intravenous levofloxacin with oral levofloxacin.
This patient with community-acquired pneumonia has been responding well to therapy, as indicated by resolution of his fever, cough, and dyspnea by day three of hospitalization. Specific criteria for changing from intravenous to oral antibiotics include improvement in fever, cough and dyspnea and a decrease in the leukocyte count. In addition, the patient must have a functioning gastrointestinal tract and be able to take oral medication. This patient meets all criteria, and intravenous levofloxacin should therefore be changed to the oral agent. In most patients, oral therapy can usually be instituted within three days.
The unchanged chest radiograph findings are not of concern because the patient is improving by all other clinical measures. Only about two thirds of patients demonstrate chest radiographic clearing of pneumonia by the fourth week of therapy. In addition, radiographic clearing is generally slower in patients who are older than 50 years of age, have multilobar involvement, or have an underlying chronic disease or alcoholism.
Neither a CT scan nor bronchoscopy is indicated because the patient is responding to therapy. However, one or both of these procedures may be required in someone who is not responding adequately to treatment. Since this patient is doing well on levofloxacin, there is no reason to switch to or add another antibiotic.
- Hospitalized patients with community-acquired pneumonia can usually be changed from an intravenous to an oral antibiotic regimen when fever, cough and dyspnea have resolved; oral intake is satisfactory; and the leukocyte count is returning towards normal.
Correct answer: E. Yersinia pestis.
This patient most likely has pneumonic plague that is caused by inhalation of the bacterium Yersinia pestis. Two to four days after aerosol release of the bacterium, patients develop headache, high fever, dyspnea, myalgias, hemoptysis and sepsis. Sputum is classically described as “watery” but may be blood-tinged. The pneumonia, which appears as a patchy bronchopneumonia on chest radiographs, can progress rapidly and culminate in stridor, cyanosis, and death. The mortality rate for pneumonic plague approaches 100% if patients are not treated with streptomycin within 24 hours of development of symptoms (ceftriaxone and erythromycin are ineffective against Y. pestis).
Anthrax, caused by Bacillus anthracis, stains gram-positive rather than gram-negative. Although the prodrome of Q fever, caused by Coxiella burnetii, is similar to pneumonic plague, the incubation period for Q fever is much longer (typically one to two weeks), and blood cultures would not grow any organisms. Haemophilus influenzae infection, especially infection caused by nontypable strains, can result in pneumonia in adults. The presentation is also similar to pneumonic plague, and blood specimens also show gram-negative rods. However, the rods are small and do not stain well. In addition, sputum is purulent rather than watery. Tularemia, which is caused by Francisella tularensis, has a similar onset of three to five days after exposure. However, pneumonitis or a pleuropulmonary process usually results. Pulmonary signs may be minimal or absent on physical examination. In addition, chest radiographs typically show perihilar lymphadenopathy and pneumonia that appears out of proportion to the patient's symptoms.
- Patients with pneumonic plague typically present with high fever, headache, myalgias, dyspnea, hemoptysis, and watery sputum.
- Patients with pneumonic plague have a mortality rate approaching 100% if not treated with streptomycin within 24 hours of development of symptoms.
Correct answer: B. Daily hemodialysis.
Daily hemodialysis is indicated in this patient. Patients with acute renal failure in surgical and medical intensive care units were randomized to management with daily hemodialysis versus every other day hemodialysis. In this study, hospital mortality was only 28% in those who received daily hemodialysis compared with 46% in those treated every other day (P=0.01). In addition, resolution of acute renal failure occurred in 9 ± 2 days in the patients given daily hemodialysis. Although commonly used in management of oliguria to help to “convert” to nonoliguric renal failure, furosemide has not been shown to alter clinical outcomes in patients with anuric renal failure. Bicarbonate infusions can eventually worsen intracerebral acid-base status by conversion via carbonic anhydrase, and acidosis does not cause its neurotoxicity or cardiotoxicity until it is very severe.
Fenoldopam is approved for hypertensive urgency but not for anuric acute renal failure. It is possible, but not yet proven, that continuous renal replacement therapy (CRRT) such as continuous venovenous hemodialysis or continuous arteriovenous hemodialysis might be superior to daily hemodialysis; a pivotal, multi-center clinical trial is under way and incomplete.
- Daily hemodialysis has been shown to significantly reduce in-hospital deaths in patients with acute renal failure in surgical and medical intensive care units.
Correct answer: E. Continue levofloxacin.
Penicillin resistance is categorized as either intermediate-level resistance (minimal inhibitory concentration [MIC] for penicillin between 0.1 and 1 µg/mL) or high-level resistance (MIC for penicillin >1 µg/mL). In the United States, more than 40% of patients with Streptococcus pneumoniae infection are infected with strains that have some level of antibiotic resistance. Although organisms that are resistant to penicillin are often associated with in vitro resistance to other antibiotics, these organisms generally remain sensitive to fluoroquinolones and are uniformly sensitive to vancomycin and linezolid.
This patient required hospitalization for community-acquired pneumonia and was appropriately started on intravenous levofloxacin as initial empiric antibiotic therapy. Although she was later found to have bacteremic pneumococcal pneumonia caused by an organism with intermediate-level resistance to penicillin, her fever curve is improving following initiation of levofloxacin, which should be active against this strain. The current therapy should therefore be continued until she fulfills the criteria for changing to oral antibiotic agents. In addition, the presence of bacteremia does not affect either the type or duration of antibiotic therapy.
Although not included in the options, ceftriaxone and cefotaxime are also appropriate for treating pneumococcal pneumonia caused by strains with reduced susceptibility to penicillin if the MIC for either agent is less than 2 µg/mL.
- Penicillin resistance is categorized as either intermediate-level resistance (minimal inhibitory concentration [MIC] between 0.1 and 1 µg/mL) or high-level resistance (MIC >1 µg/mL).
- Organisms that are resistant to penicillin generally remain sensitive to fluoroquinolones and are uniformly sensitive to vancomycin and linezolid.
Correct answer: A. Mycobacterium avium complex hypersensitivity pneumonitis.
The patient has a subacute illness that could be either pneumonia or pulmonary hypersensitivity. The overwhelming likelihood is that her illness is related to hot tub exposure and that an aerosol of Mycobacterium avium complex (MAC) is causing hypersensitivity pneumonitis. MAC is present in the water supply in most areas of the United States, which explains why people who use hot tubs (and, less frequently, showers) sometimes develop this form of hypersensitivity pneumonitis. What is not understood is why more people do not develop this infection.
Although the patient's pulmonary function tests are somewhat abnormal, she does not have tuberculosis because of the normal chest radiograph. Nocardia species can cause pneumonia. However, the most common Nocardia lung syndrome is nodular and tends to occur in patients with defects in cell-mediated immunity. Infection with Rhodococcus species is a rare cause of pneumonia in patients with reduced cell-mediated immunity and does not induce bronchitis. Although contamination of the sputum sample is possible, the clinical presentation is quite consistent with MAC hypersensitivity pneumonitis.
- Mycobacterium avium complex hypersensitivity pneumonitis is associated with use of hot tubs.
- Mycobacterium avium complex is present in the water supply in most areas of the United States.
Correct answer: C. Hyponatremia.
Hyponatremia is a common and dangerous cause of delirium in hospitalized patients. Undernourished elderly patients are at particularly high risk for this condition and should always be checked when they may be susceptible to hyponatremia and exhibit changes in their mental status.
Meningitis may accompany pneumonia; however, because this patient has responded to treatment and has been afebrile for 2 days, he is unlikely to be experiencing meningitis at this late date. In addition, he has no physical examination findings indicative of meningitis. Alcohol abstinence syndrome is always a consideration when delirium develops without a clear explanation in a hospitalized patient. Minor withdrawal symptoms and seizures usually occur within 6 to 36 hours of abstinence, whereas delirium tremens is a late occurring event, occurring 48 to 96 hours after alcohol cessation. This patient's symptoms are occurring too late for alcohol withdrawal syndrome, but the timing is compatible with delirium tremens; however, delirium tremens is characteristically accompanied by tachycardia, agitation, tremulousness, and mild fever, which are notably absent in this patient.
When hypoxemia leads to delirium, the patient is often agitated rather than drowsy. Furthermore, it would be unusual for a patient to have normal vital signs with newly worsening hypoxemia. Antibiotic therapy rarely causes drug-induced delirium.
- Undernourished elderly patients are at particularly high risk for hyponatremia, a common and dangerous cause of delirium.