This study analyzes a large cohort of 959 patients admitted to our hospital for CAP over a period of several years. Our trial confirms the diagnostic usefulness of determining the UPA content in concentrated urine. In our experience, this noninvasive, rapid, and simple technique increases the diagnostic yield compared to conventional diagnostic methods. The test enables quicker initiation of therapy with the appropriate antibiotics. Consequently, this method has the potential to shorten patient hospital stays and reduce CAP mortality rates (11
Given the diagnostic difficulties associated with CAP, blood culture results were viewed as the gold standard, providing 81% sensitivity (46 antigen-positive patients of the definitive 57 CAPP). These results are similar to results obtained in other studies with sensitivity rates between 77 and 82% (6
); all listed studies calculate sensitivity with regard to the definitive diagnosis of CAPP. On the other hand, our study results differed from the sensitivity rate of 66% reported by Rosón et al.; this is probably explained by the fact that those authors considered CAPP cases not only those with positive blood culture and/or pleural fluid culture but also those with positive Gram staining and sputum culture (27
In our study, only probable CAPP cases were considered and included in our sensitivity calculation. If our study had considered positive sputum culture as a CAPP diagnosis and the gold standard, in spite of the obvious limitations regarding collection difficulties and occasional poor validity (26
), our sensitivity rate would have fallen to 67%, similar to that of Rosón et al. (27
). Furthermore, our study sensitivity rate clearly conflicts with the 100% reported by Marcos et al. (22
). In our experience, the sensitivity of the ICT test differs for definite pneumococcal pneumonia versus probable pneumococcal pneumonia. This differential sensitivity might be due to the fact that, due to our definition for definite pneumococcal pneumonia, 89% of these patients were bacteremic, whereas none of the probable pneumococcal pneumonias were bacteremic. Bacteremic pneumococcal pneumonia might be more likely to produce positive urine antigen tests than nonbacteremic pneumonia. The specificity of the ICT varies depending on different studies. Domínguez et al. (6
) recorded 97% specificity (two false positives in 71 patients with confirmed etiologic pneumonia were caused by a microorganism other than S. pneumoniae
). This high specificity rate may be due to the fact that Domínguez et al. not only used blood culture as the gold standard for CAPP but also used the laborious contraimmunoelectrophoresis method for antigen detection of 84 urinary S. pneumoniae
serotypes. Consequently, the percentage of CAPP diagnoses increased, and the number of false positives usually found in clinical practice decreased. Murdoch et al. studied 169 control in-patients without infectious pathology and found no positive cases, thus obtaining 100% specificity (23
). On the other hand, Smith et al. (31
) determined the UPA content in 106 patients with nonpneumonic bacteremia and found three positives, which gave a 97% specificity.
In view of these conflicting results (possibly due to different methodologies), we decided to calculate specificity in diverse groups. We assessed test specificity in cases with a definitive etiologic diagnosis other than S. pneumoniae
, and we obtained 80% specificity, a specificity lower than the percentages reported in other studies (6
). These results are not wholly reliable since some of the cases that were considered false positives may really have been hidden pneumococcal pneumonia, which cannot be diagnosed by other means. It has been calculated that one-third of the CAP cases that do not have an etiologic diagnosis are pneumococcal (7
) or that some CAP cases considered to have other etiologies in fact have a mixed nature with pneumococcal participation. It has been estimated that more than 10% of the CAP cases are of polymicrobial etiology. We must point out that there is a great debate regarding whether these patients have sequential (viral or atypical infection, followed by pneumococcal) or concomitant polymicrobial pneumonia. In the present study, the most common pathogens in the known etiology groups with positive UPA are listed in Table .
In view of this, and bearing in mind that it is nearly impossible to ascertain the exact number of CAPP cases due to diagnostic difficulties and the high frequency of mixed CAP, another more reliable possibility would be to calculate the specificity in subjects without CAP. To calculate this, we evaluated two different groups of patients. The first group consisted of patients with prior respiratory pathology (COPD and asthma); the second group consisted of patients in the hospital for diverse fractures awaiting surgery. The group of patients with COPD and asthma were considered because of the considerable frequency of pneumococcal carriers among these patients and the possibility of nonpneumonic infection exacerbation, which would make the specificity study more useful in these cases (24
). UPA was detected in 12 of the 155 cases of COPD and asthmatic patients, yielding a specificity of 92%. The 12 false positives were found in patients with exacerbated COPD, which, in our experience, makes it advisable to evaluate a positive ICT result with caution due to the possibility of colonization of S. pneumoniae
and the persistence of ICT in such patients. These conclusions have previously been reported in other studies (22
). Any patient in the COPD control group with a positive UPA had fever and/or purulent sputum. Using computed tomographic scans, posthidratation infiltrates were not observed in any case.
The specificity was 99% for the 80 patients hospitalized for diverse fractures and who did not have clinical infections. Only one case tested as antigen positive. This patient had manifestations of respiratory infection the month before, which had not required hospitalization and which could have conditioned a persistence in UPA. The data obtained from this group are similar to those in the study by Murdoch et al., who also used controls without infectious pathology (23
). Therefore, the calculation of specificity presents difficulties because it involves CAP with nonpneumococcal etiology, which could in fact be of mixed etiology. As a consequence, when using COPD patients without CAP, there will probably be colonization and/or UPA persistence from previous respiratory infections.
In our cohort only a small percentage, 6%, was diagnosed with CAPP when CMM were used, whereas 26% were diagnosed with CAP without an etiologic diagnosis after testing antigen positive. Therefore, the use of ICT in urine should increase the diagnosis of CAPP from 6% (57 cases) to 32% (290 patients) compared to CMM. Clearly, the use of ICT should increase the diagnostic yield in CAPP and the percentage of overall etiologic diagnoses in the cohort from 28 to 49%. Given the absence of a gold standard with good sensitivity (blood culture is considered to be positive in only 15 to 40% of CAP cases [19
]), the precise significance of these results cannot be assessed.
We believe the present study has some limiting factors, including the following: (i) previously discussed difficulties in calculating the specificity of the technique in the pneumonia group (the gold standard is of limited sensitivity and prevents research into the negative and positive predictive values of the technique); and (ii) possible repercussions of previous antibiotic treatment on the usefulness of the technique have not been studied in this article, nor have the possible connections between development time of CAP and test results. Both of these factors could affect the usefulness of the technique, and we will address them in a future study.
In our experience, this noninvasive technique is a useful test from the clinical viewpoint for diagnosing CAPP, especially in nonbacteremic manifestations (less frequently diagnosed). The test is rapid and simple and has good sensitivity and specificity. It is complemented by CMM, making possible an increased rate of etiologic diagnosis of CAPP and expediting the initiation of appropriate antibiotic treatment upon hospital admission. On the other hand, the interpretation of results requires greater caution with COPD patients. We believe new studies are needed to analyze the persistence of UPA in patients with recent CAP and in patients with probable pneumococcal colonization.