to cross-react with antibodies to the vaccine serotypes. It should be noted that in the pre-antibiotic era, mortality from invasive pneumococcal disease was 80%. It now stands at between 10 and 20%. With increasing resistance limiting the efficacy of antimicrobials, will mortality due to invasive pneumococcal disease begin to increase?
6. There are four potential explanations for why patients can have repeated episodes of infection with the same serotype. The first three fall under the category of inadequate treatment; the fourth involves reinfection.
In terms of inadequate treatment, the patient may have been treated with an antimicrobial to which the infecting organism was not susceptible. Given the increasing trend of multidrug resistance in pneumococci, this is a reasonable explanation. Susceptibility testing of this organism revealed it to be pan-sensitive, meaning it was susceptible to all antimicrobials against which it was tested, including the antimicrobial with which he was treated. The second explanation is that the patient did not receive antimicrobials for a sufficient period of time to eliminate the organism. If hospitalized, it is likely that the patient would receive appropriate antimicrobial therapy during his stay. However, in the managed care era, hospital stays are becoming shorter and shorter. Our patient received 4 days of intravenous antimicrobials in the hospital and then oral antibiotics prescribed for use after discharge. If he failed to take his oral antibiotics, i.e., was noncompliant, his infection may have been inadequately treated, contributing to a relapse. A third possibility is that he had an undrained focus of infection that the antimicrobials did not adequately penetrate. In pneumococcal pneumonia, highly viscous pleural exudates may form that antimicrobials cannot penetrate. Removal of these exudates by drainage may be required for treatment of severe infections. Occasionally, drainage of exudates is not possible percutaneously. In these cases, a surgical procedure may be necessary to remove this focus of infection.
The fourth possible explanation is reinfection with the same serotype. Serotype 23 is one of the most common serotypes of S. pneumoniae, being responsible for 7% of invasive pneumococcal infections in a recent U.S. survey. It is possible that he was carrying the organism in his nasopharynx and became reinfected in that manner, since it has been shown that antimicrobial therapy does not reliably eliminate nasopharyngeal colonization of pneumococci. What is more difficult to understand is why his original infection did not result in his mounting a protective immune response to this organism. A possible explanation is that his immunosuppressed state due to the carcinoma blunted his immune response. It is uncertain if vaccination would be an effective preventive strategy in this patient given the observation that he had three infections in a month with S. pneumoniae serotype 23, which is present in the vaccine.
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CASE 9
The patient was an 18-day-old female who at initial presentation was brought to the emergency department by her mother after a 3-day bout of coughing. Her mother also reported that her daughter had been “spitting up” more than usual and had episodes of tachypnea. During the initial exam, a rapid respiratory syncytial virus test was obtained with negative results. A review of systems was notable only for a nonproductive cough. Her pulse was 168 beats/min, her respiratory rate was 32 inspirations per minute, and oxygen saturation was 92 to 95% on room air. Her complete blood count was significant for a white blood cell count of 15,300 cells/μl with an absolute lymphocyte count of 10,900 cells/μl. The mother had a chronic cough of 4 weeks’ duration but had been afebrile. Six weeks before this patient’s admission, her 10-year-old brother also had a prolonged coughing illness that responded to breathing treatments and inhaled steroids.
After initial examination, the child was admitted to the hospital. Her initial hospital course was uneventful, and she was discharged after 2 days. However, she was readmitted the following day with worsening respiratory symptoms. Over the next several days she had increasing difficulty breathing, tachypnea up to 100 breaths per minute, and oxygen saturations in the low 80s during coughing episodes. She was admitted to the pediatric intensive care unit for respiratory support. She had an extremely complicated and prolonged intensive care unit course that included pulmonary hypertension, acute respiratory distress syndrome, and health care-associated pneumonia. After a 10-week hospital stay, she was eventually discharged to return home, where her recovery was uneventful.
1 1. Nucleic acid amplification testing (NAAT) was performed on a nasopharyngeal swab. The amplified DNA was screened for a particular agent with positive results, and the patient was begun on azithromycin. What was the etiologic agent infecting this patient? What findings in this case support this conclusion?
2 2. Why is a nasopharyngeal specimen superior to any other clinical specimen for diagnosing this infection? Why has NAAT replaced culture for the diagnosis of this pathogen?
3 3. Describe the clinical course of this disease. Why didn’t the patient respond to the antimicrobial she was given?
4 4. What about the pathogenesis of this disease puts this patient at increased risk for health care-associated pneumonia?
5 5. A vaccine exists to prevent infections such as the one in this patient. Explain why and how this patient was infected. What does this case tell you about the vaccine? Vaccine strategies for preventing infections with this organism have recently changed. What changes in the vaccine are making better prevention possible? In particular, what groups
