beats/min, blood pressure of 154/107 mm Hg, and pO2 of 92 mm Hg. Chest auscultation revealed coarse breath sounds at the left lower base with bibasilar fine crackles. He was found to have a left lower lobe infiltrate on chest radiograph. His admission white blood cell count was 10,600/μl with 70% neutrophils, and his hemoglobin was 9.4 g/dl. Sputum Gram stain at admission revealed >25 polymorphonuclear cells and >25 squamous epithelial cells per low-power field. Because of the high numbers of squamous epithelial cells, the specimen was not processed further. Two blood cultures obtained at admission were positive for the organism seen in Fig. 8.1. The Gram stain from the blood culture bottle is shown in Fig. 8.2.
The patient was admitted to the hospital and treated with ceftriaxone intravenously. Upon defervescence, he was discharged on a regimen of oral azithromycin based on the organism’s identification and antimicrobial susceptibility results. Of note: this was the patient’s third episode of this illness in the past month. Isolates from all three episodes belonged to the same serotype, type 23.
1 1. What disease process was ongoing in this patient? What clinical prediction rules could be applied to this patient in determining whether he should be hospitalized? Why do you think the decision was made to hospitalize him?
2 2. What organism was causing this individual’s infection?
3 3. What other patient populations are at risk for infection with this organism?
4 4. Two different virulence factors produced by the organism infecting this patient are important in disease pathogenesis. What are they, and what role do they have in the pathogenicity of this organism?
5 5. What strategies are available to prevent infections with this organism? Why are preventive strategies becoming of greater importance with this organism?
6 6. How do you explain the patient’s having repeated episodes of infection with the same serotype of this organism? There are at least two and possibly more explanations.
CASE 8 CASE DISCUSSION
1. Based on his physical findings of productive cough with purulent sputum, shortness of breath, fever, and bibasilar fine crackles on chest auscultation in the left lower lung, coupled with left lower lobe infiltrates on radiographic imaging, this patient had a lower respiratory tract infection most consistent with bacterial pneumonia. Because this patient was at home at the time of disease onset, he would be considered to have community-acquired pneumonia.
Two clinical prediction models are widely used to determine if patients with community-acquired pneumonia should be admitted to the hospital. Having metrics for this purpose is valuable because patients do not wish to be hospitalized. There are several reasons for this: they get better faster at home; they are not exposed to nosocomial risks, including infections; and it is more cost-efficient. These two models allow for a rational approach to this process. The pneumonia prediction rule is a scoring system based on demographics; coexisting conditions; and physical, laboratory, and radiographic findings. Because of its complexity, it is more of a research tool with limited practical application. The second system is CRB-65, a modification of CURB-65. CRB-65 is simple to use, as it has four criteria that can be easily determined: C, presence or absence of confusion; R, respiratory rate of >30 per minute; B, low systolic (≤90 mm Hg) or diastolic (≤60 mm Hg) blood pressure; and age >65 years. Patients are ranked on a scale of 0 to 4; those with a score of 3 or 4 are judged to have severe disease, with frequent admission to the intensive care unit and 30-day mortality of >40%. This patient had a CRB-65 score of 0. Patients with that score are usually not admitted to the hospital, as their 30-day mortality is 0%. However, CRB-65 is a simple system that does not take into account certain complexities in this patient. This patient was immunocompromised due to his history of head and neck carcinoma. He also had a long-term smoking history, which put him at increased risk for respiratory infections. Finally, he had previous episodes of respiratory infection, which were concerning to his physician; thus the decision to admit him.
2. In patients who are suspected of having bacterial pneumonia, attempts are made to determine the etiologic agent so that management can be directed toward a specific agent. In lobar pneumonia, as was seen on physical and radiographic examination of this patient, the most common etiologic agent is Streptococcus pneumoniae. Three approaches are widely used to determine if a patient is infected with this organism: sputum examination, blood culture, and pneumococcal urinary antigen detection. The organism isolated from this patient’s positive blood culture was a catalase-negative, Gram-positive diplococcus (Fig. 8.2). It was alpha-hemolytic on sheep blood agar and was susceptible to the copper-containing compound optochin (ethylhydrocupreine hydrochloride). These phenotypic characteristics are consistent with S. pneumoniae. Approximately one-third of patients with pneumococcal pneumonia will have a positive blood culture, so the finding in this patient was consistent with this diagnosis. Pneumococcal pneumonia can often be diagnosed by its characteristic Gram stain, in which stained sputum demonstrates numerous polymorphonuclear cells and the presence of many lancet-shaped, Gram-positive diplococci. However, it requires a high-quality specimen, which is defined as one where there are ≥25 neutrophils and <10 squamous epithelial cells per low-power field. In patients with high-quality specimens who have not received antimicrobials prior to specimen collection and have characteristic Gram-positive diplococci, Gram stain has a sensitivity of 80%. However, in the clinical setting, it is not uncommon to receive poor-quality sputum specimens that are unable to be analyzed, as was the case for this patient. Poor-quality specimens typically have high numbers of squamous epithelial cells because of contamination of the specimen with oropharyngeal secretions. Oropharyngeal secretions contain high numbers of squamous epithelial cells. Because the pneumococcus can be part of the resident microbiota of the oropharynx, the finding of this organism in a poor-quality sputum specimen cannot be reliably associated with the diagnosis of pneumococcal pneumonia. Such a finding may be a false positive.
Another test for invasive pneumococcal disease is a urinary antigen test. This test is most likely to be positive in patients with bacteremic pneumococcal pneumonia, the exact clinical situation seen in this patient. This test is most useful in a setting where antimicrobials have already been given, making it much less likely that organisms will be detected either by blood or sputum culture. Urinary antigen tests should not be used in children, especially in the winter months, since false positives due to high colonization rates may occur.
3. Many different patient populations are at increased risk for invasive pneumococcal disease—pneumonia, bacteremia, and meningitis. Patient populations in whom rates of pneumococcal invasive disease are increased include AIDS patients; patients who are anatomically or functionally asplenic (including patients with sickle-cell disease); patients with cardiovascular, liver, or kidney diseases; individuals with diabetes or malignancies; and individuals who are receiving immunosuppressive agents because of connective tissue disease or organ transplantation. Prevention strategies that target these populations are discussed in the answer to question 5.
4. The polysaccharide capsule is the major virulence factor of S. pneumoniae. More than 90 antigenically different capsular polysaccharides have been recognized, with 7 types—4, 6B, 9V, 14, 18C, 19F, and 23F—being responsible for 80 to 90% of cases of invasive pneumococcal disease. Animal experiments done in the first part of the 20th century established the importance of capsule in the organism’s ability to cause