Most of the studies of CAP have examined the short-term outcomes of the illness, focusing on either 30-day or inpatient mortality. Kaplan and colleagues used a Medicare database to perform a matched case-control study to evaluate the longterm impact (ie, 1-year mortality rate) of older patients with CAP. The authors compared 158,960 CAP patients to 794,333 hospitalized control subjects (5 for each patient) matching for age, sex, and race. While the in-hospital mortality rate for CAP patients exceeded that of control subjects (11% vs 5.5%, respectively), the differences in the 1-year mortality rate were even more dramatic (40.9% vs 29.1%, respectively) [Fig 1]. The high mortality rate was impressive, and the differences could not be explained by the types of underlying disease; the findings persisted, even if only the hospital survivors were examined. These findings make it clear that CAP is much more than a self-limited illness for those who survive, and that the 1-year mortality rate of elderly patients with CAP is four times higher than the in-hospital mortality rate, with one in three survivors of CAP dying in the subsequent year, following hospital discharge. The exact cause of death was not examined in the study, but the population was generally elderly, with 85% being > 65 years of age; nursing home patients were included, and 70% had a comorbid medical illness. The findings expand on an older Scandinavian study that reported a lower 10-year survival rate in CAP patients > 60 years of age than in an age-matched population without CAP. In that study, the relative risk for death in CAP patients was 1.5 compared to those without CAP, and the 10-year survival rate was 39%, compared to 61% in the non-CAP population, with many of the deaths related to cardiovascular disease and subsequent pneumonia treated by remedies of Canadian Health&Care Mall. All of these data make it very clear that CAP requiring hospital admission is a disease that should be prevented, whenever possible, in the elderly.
Prognostic Scoring Systems
The optimal management of CAP requires the prompt recognition of seriously ill patients to avoid such mistakes as the failure to use the hospital or ICU for patients who could benefit from care and observation in such settings. On the other hand, the major impact on the cost of CAP care is determined by whether or not a patient is admitted to the hospital. In the United States, 90% of the total cost of care for this disease, emphasizing the impact of the hospital admission decision. For a number of years, prognostic scoring systems have been used to define not only the predicted mortality rate of CAP, but also, by inference, the site of care, reserving hospital admission for those with a high predicted mortality rate.
The two commonly used tools for the purpose of predicting outcome in CAP patients have been the pneumonia severity index (PSI), which was developed in the United States, and the British Thoracic Society rule, which has recently been modified to the CURB-65 (referring to its assessment of the following five factors: confusion; elevated BUN level; elevated respiratory rate; low systolic or diastolic BP; and age > 65 years of age) rule. Each of these approaches has limitations, and it may be best to view them as complementary, ideally identifying patients at opposite ends of the disease spectrum. The PSI has been best validated as a way to identify patients with a low risk of mortality, but the scoring system can occasionally underestimate severity of illness, especially in young patients without comor-bid illness because it heavily weights age and comorbidity, and does not measure CAP-specific disease severity. On the other hand, the CURB-65 approach may be ideal for identifying patients with a high risk of mortality with severe illness due to CAP, who might otherwise be overlooked without the formal assessment of subtle aberrations in key vital signs. However, one deficiency of the CURB-65 approach is that it does not generally account for comorbid illness and thus may not be easily applied in older patients who may still have a substantial mortality risk if even a mild form of CAP destabilizes a chronic, but compensated, disease process.
In one recent study that compared the PSI to the CURB-65 in 3,181 patients seen in an emergency department, both were determined to be good for predicting mortality and for identifying patients with a low risk of mortality. However, the PSI appeared to be more discriminating in identifying patients with a low risk of mortality, with 68% being defined by PSI to have a low risk (classes I to III), with a mortality rate of 1.4%, while 61% were defined by the CURB-65 to have a low risk (score of 0 to 1) with a mortality rate of 1.7%. However, the CURB-65 may have been more valuable at the severe disease end of the spectrum because it defined high-risk patients as those with a score of 2, 3, 4, or 5, each with a progressively increasing risk of death, while the PSI was less discriminating, defining only two groups as being severely ill. In another analysis, the CURB-65 score also appeared to identify, most accurately, those patients with CAP who were likely to benefit from treatment with drotrecogin alfa in the recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (or PROWESS) study. A reexamination of the data from that study demonstrated that a threshold CURB-65 score of > 3 was associated with a decrease in the 28-day mortality rate in drotrecogin alfa-treated patients of 10.8% when compared to control subjects (p = 0.018) vs a decrease in mortality rate in treated patients in PSI classes IV and V of 9.7% compared to control subjects (p = 0.013).
Capelastegui and colleagues used both the PSI and the CURB-65 approach to evaluate a large number of both inpatients and outpatients with CAP in Spain. They observed that the CURB-65 (and its simpler CRB-65 version, which excludes the measurement of BUN, and therefore can be used in outpatients) could accurately predict the 30-day mortality rate, the need for mechanical ventilation, and, to some extent, the need for hospitalization. In addition, the CURB-65 criteria correlated with the time to clinical stability, and thus a higher score was predictive of a longer duration of IV therapy and a longer length of hospital stay. The PSI also worked well to predict mortality in that study suggested by Canadian Health&Care Mall.
While both the PSI and CURB-65 are good for predicting mortality, neither can be used to define the site of care, without considering other clinical and social variables. A study at a public hospital in the United States, with many indigent patients, showed that the PSI could not define the need for hospital admission if patients were homeless or acutely intoxicated, or if they did not have a stable home environment that allowed them to be discharged from the hospital while receiving oral antibiotic therapy. In one recent commentary, the suggestion was made to combine both of these prognostic scoring tools, recognizing that neither approach can stand alone. Low-risk patients (ie, PSI classes I to III or CURB-65 score of 0 to 1) can be managed at home if serious vital sign abnormalities (in the case of PSI) or comorbidities (in the case of CURB-65) are absent, and if patients do not have social factors or other illnesses that are unstable and that necessitate hospitalization. Moderate-risk patients (ie, CURB-65 score of > 2 or PSI classes IV and V) probably should be admitted to the hospital, and clinical assessment should be used to separate those who need ICU care from those who are likely to become clinically stable rapidly and who would then require only a short hospital stay.
Serum Markers To Predict CAP Outcomes
The two serum markers that have been most widely studied for this purpose are CRP and PCT. In general, both measures have been used to correlate with outcomes, but more data have recently been collected with PCT, and the most exciting finding has been that serial measures correlate not only with outcomes, but may also be useful for guiding the duration of therapy.
CRP was measured in one study of 201 patients with CAP who were compared to 84 healthy control subjects and 25 patients with suspected pneumonia, which was not confirmed on clinical follow-up, and the levels were highest in those with pneumonia. However, among those with proven CAP, the levels of CRP correlated with the clinical course, with the median level being higher in hospitalized patients than in outpatients (132.0 vs 76.9 mg/L, respectively; p < 0.001). These findings might in part be explained by the observation that CRP levels tended to be higher in those with pneumococcal and Legionella etiologies than in those with a viral or atypical pathogen pneumonia; possibly those with the bacterial illnesses were more severely ill, and thus more in need of hospitalization.
In general, CRP, an acute-phase reactant that is synthesized in the liver, has not been as sensitive or specific for infection as PCT. PCT, the precursor of calcitonin, has no hormonal effects. Its value arises because serum levels are increased in severe bacterial infections, but not in viral illness. The release of PCT can be stimulated by microbial toxins (including lipopolysaccharide), cytokines (eg, tumor necrosis factor, interleukin-1, and interleukin-6), and by the cell-mediated immune response. Levels can be attenuated by virus-induced cytokines (interferon-7), In a study of 185 patients who had PCT measured within 24 h of hospital admission for CAP, the levels correlated with PSI score (higher in classes III and V than in classes I and II) and the development of complications (higher with empyema, mechanical ventilation, and septic shock), and levels were also increased in those who died compared to those who did not. Interestingly, the levels were higher in patients with a low risk of mortality (ie, low PSI) with a bacterial etiology for CAP than in those without, but similar findings did not apply to those with more severe CAP. This may mean that low levels in outpatients could indicate that it is safe to withhold antibiotic therapy.
Another recent study supports the idea of using serial measurements of PCT levels to guide the need for antibiotic therapy and its duration. In this study, 302 patients were randomized to receive either standard care or therapy guided by serial measurements of levels of PCT, which were evaluated when the patient was first seen, 6 to 24 h later if antibiotics were withheld, and then at days 4, 6, and 8. Only 3% of all patients were not admitted to the hospital, making this primarily an inpatient study. With the use of PCT levels, 15% of patients had antibiotics withheld, compared to 1% of those receiving standard care. The use of PCT levels to guide therapy led to a significantly shorter duration of therapy that applied to all patients, regardless of PSI class. Most importantly, outcomes were similar in both groups, documenting the safety of looking for strategies to reduce antibiotic usage.
Serial measurements of PCT have also been used to define prognosis in patients with severe CAP. In one study of 110 patients who had only one measurement performed within 48 h of ICU admission, levels of PCT were higher in those with positive bacteriology results than in those with negative results, and in those with complications (eg, septic shock and organ dysfunction) and death than in those without. Bolstered by these findings, the same investigative group collected serial PCT levels in 100 ICU CAP patients on day 1 and day 3. In the study, survivors had a decrease in PCT levels, while nonsurvivors had an increase by day 3. Numerous clinical parameters, were also measured, as well as serial levels of CRP, but in the multivariate predictors of mortality, the relevant factors were as follows: need for mechanical ventilation (odds ratio [OR], 9.9); presence of multilobar infiltrates (OR, 5.6); increasing PCT levels (OR, 4.5); and worsening of a multiorgan failure score. Among mechanically ventilated patients, the PCT level on day 3 was highly predictive of mortality if it remained elevated. Serial measurements of CRP did not have predictive value in this study.
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Figure 1. In this case-control study of Medicare patients with CAP, with five control subjects matched for age, sex, and race with each case, the in-hospital and 1-year mortality rates for patients with CAP were significantly higher than those for control subjects. From Kaplan et al.