Cases in Medical Microbiology and Infectious Diseases. Melissa B. Miller
well recognized that the capsular polysaccharide allows the pneumococcus to evade phagocytosis.
The second virulence factor is the cholesterol-dependent cytolysin, pneumolysin. Pneumolysin acts on both alveolar epithelial cells and pulmonary endothelial cells. Pneumolysin may contribute to fluid accumulation and hemorrhage by directly damaging these two cell types. Animal studies of pneumococcal pneumonia indicate that pneumolysin plays a primary role in the inflammation, fluid accumulation, and hemorrhage that occurs in the alveoli during lobar pneumococcal pneumonia. The inflammatory response is due at least in part to pneumolysin upregulating the synthesis of both tumor necrosis factor-α and interleukin-1 in the airways.
5. Currently, there are two vaccines licensed for prevention of pneumococcal disease, a 23-valent polysaccharide vaccine and a 13-valent conjugate vaccine. The 23-valent vaccine is used in adults, while the 13-valent conjugated vaccine was developed for use in children <2 years of age. Young children are not able to reliably mount a T-cell-independent immune response, the type of immune response necessary to produce antibodies against polysaccharide antigens. However, they are able to mount a T-cell-dependent immune response.
The 13-valent pneumococcal vaccine is also recommended for adults, especially immunocompromised individuals. Currently, many clinicians are still using the 23-valent vaccine in adults >60 years. In adults, the 23-valent polysaccharide vaccine has been used successfully for many years. The efficacy of the 23-valent vaccine in adults is not as high (efficacy ranges from 50 to 90% in different populations) as that of the 13-valent conjugate vaccine in children.
A conjugate vaccine is one in which a polysaccharide antigen is coupled to a carrier protein. The coupling of a polysaccharide antigen to a protein creates a “new” antigen. This new antigen stimulates a T-cell-dependent immune response (see case 45 for further details). Therefore, the conjugated pneumococcal vaccine results in a protective immune response to capsular types present in the vaccine and perhaps to other related serotypes in children <2 years old. It has been shown to be highly efficacious (>95%) in preventing invasive pneumococcal disease in this age group. It has been less effective in preventing a common pneumococcal infection in this age group, otitis media. The conjugated pneumococcal vaccine is now recommended for use in all children <2 years of age.
The widespread use of the 13-valent conjugated pneumococcal vaccine in children has resulted in declines in the two major populations with invasive pneumococcal disease: those <5 and those >65 years of age. Herd immunity clearly is playing a role in this decline and is discussed in greater detail in case 45.
An additional vaccine strategy that might be helpful in protecting this patient from pneumococcal disease would be to vaccinate him against influenza virus. Influenza infection has been recognized as being an important predisposing factor for the development of pneumococcal pneumonia.
Alternatively, prophylactic antimicrobials have been used in selected populations, such as sickle-cell patients with a history of recurrent invasive pneumococcal infections. Given the problem of emerging drug resistance in the pneumococci (see below), this is probably a preventive strategy that is becoming less efficacious.
The intense interest in pneumococcal vaccine is being driven to a significant degree by an alarming increase in the numbers of multidrug-resistant pneumococcal isolates being recovered from patients with invasive disease. Prior to 1990, pneumococcal isolates that were resistant to penicillin were quite unusual in the United States, as was the recovery of isolates that were resistant to other classes of antimicrobials. Beginning in the 1990s, pneumococcal isolates resistant to multiple antibiotics, including penicillin, macrolides, and trimethoprim-sulfamethoxazole, became increasingly common. Rates of resistance accelerated in the late 1990s. Some of this increase was due to the dissemination of selected clones of multidrug-resistant pneumococci, including the international dissemination of a multidrug-resistant type 23 strain. However, a common theme in the increasing drug resistance in this organism is the inappropriate use of antimicrobial agents. Several studies have been able to link increased use of specific antimicrobials, such as the macrolides and fluoroquinolones, with increased resistance. Because multidrug-resistant organisms are being seen with increasing frequency in invasive pneumococcal disease, it is clear that these multidrug-resistant strains have maintained their virulence, unlike some drug-resistant strains of other organisms that appear to be less virulent than nonresistant ones. Prevention of invasive infection with multidrug-resistant organisms by the two vaccines may be possible because >90% of multidrug-resistant pneumococcal serotypes are either present in the vaccines or likely 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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