Urinary Antigen Assay Research Articles

Legionellosis must be kept in mind in case of pneumonia with lung abscesses in children receiving therapeutic steroids

A 10-year-old boy, who had received recurrent short-course treatments with steroids to control severe autoimmune thrombocytopaenia, developed Legionnaires' disease as community-acquired pneumonia. Legionella pneumophila pneumonia was complicated by an extended abscess of the right inferior lobe, leading to residual lung cavities. Legionellosis must be kept in mind as the differential diagnosis in the case of severe pneumonia and with lung abscesses in children receiving therapeutic steroids. Legionella-specific diagnostic tests (polymerase chain reaction [PCR] in respiratory samples or urine antigen assay) and, also, specific empirical antibiotic combination therapy are required for the early detection and treatment of L. pneumophila pneumonia in childhood.

Legionella pneumophila

Legionellae are environmental bacteria that can be frequently isolated from technical water supply systems. The most prevalent species is Legionella pneumophila, especially serogroup 1. In the environment, legionellae multiply in amoebae. Since Legionella pneumonias cannot be distinguished from pneumonias caused by other microbial pathogens, special microbiological tests, e.g., urinary antigen assays, are essential to detect Legionella infections. All water supply systems to which the patient is exposed during the incubation time of 2 to 10 days might be the source of the infection. This can be confirmed or excluded by molecular typing of isolates from patients and the environment. The most commonly used techniques are monoclonal antibody typing and sequence-based typing (SBT). Some sequence types (ST) are frequently found among clinical strains but are seldom isolated from the environment, e.g., ST 23, 42, 47, 62, and 146. It is safe to assume that such strains are highly virulent. Conversely, it does not seem to be justified to dedicate the same awareness to all environmental Legionella strains.

Clinical impact of combined viral and bacterial infection in patients with community-acquired pneumonia

New methods for identifying respiratory pathogens have led to several reports of a high yield of mixed infections in patients with community-acquired pneumonia (CAP). The clinical impact of these findings has, however, not been fully evaluated. We aimed to compare patients with a pure bacterial etiology with those with findings of both bacteria and virus regarding severity of illness and length of hospital stay. Adults with CAP admitted to Karolinska University Hospital were studied prospectively (N = 184). Microbiological methods included cultures from blood, sputum and nasopharyngeal secretions; sputum samples analyzed with quantitative real-time polymerase chain reaction for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed with polymerase chain reaction and serology for Mycoplasma pneumoniae, Chlamydophila pneumoniae and viruses common in the respiratory tract; and urine antigen assays for detecting pneumococcal and Legionella pneumophila antigens. The pneumonia severity index (PSI) was used to assess the severity of illness. The likelihood of getting a score corresponding to PSI classes IV or V was higher in patients with findings of both bacteria and virus than in those with a bacterial pathogen alone (odds ratio 4.98, 95% confidence interval 2.09-11.89; p < 0.001). The median length of hospital stay was 7 days among patients with mixed infections and 4 days among those with a bacterial etiology alone (p = 0.018). Patients infected with a virus and a bacterial pathogen more often develop severe CAP and have a longer hospitalization than those with a bacterial etiology alone.

Pneumococcal Vertebral Osteomyelitis and Psoas Abscess in a Patient with Systemic Lupus Erythematosus Disclosing Positivity of Pneumococcal Urinary Antigen Assay

A 53-year-old woman with systemic lupus erythematosus presented with a 3-day history of fever and coughing. Diagnosis of pneumococcal bronchitis was made based on symptoms and positivity of pneumococcal urinary antigen test. On day 3, severe low back pain acutely occurred. Pneumococcal vertebral osteomyelitis and psoas abscess was diagnosed 17 days later by yield of penicillin-susceptible S. pneumoniae strain in blood cultures and drainage fluid. Although pneumococcal urinary antigen test is a useful tool for the diagnosis of pneumococcal pneumonia, we should consider the possibility of pneumococcal infections other than pneumonia or overwhelming bacteremia in immunosuppressive patients when urinary antigen test is positive.

Legionnaires' Disease with Facial Nerve Palsy

Legionnaires' disease is primarily a pneumonic process caused by Legionella pneumophilia, a gram-negative aerobic bacillus but also has multiple system involvement. The most common manifestation is encephalopathy suggesting a generalized brain dysfunction but focal neurological manifestations have been reported. We report a patient with Legionella pneumonia associated with cerebellar dysfunction and unilateral facial nerve weakness. 51-year-old previously healthy male presented with shortness of breath, cough, slurred speech, and unsteadiness on feet associated with malaise, fevers and myalgias. Patient's family reported facial asymmetry for 2 days. Patient had no significant medical history and was not on any medication. He denied smoking, alcohol or illicit drug use. Chest X-ray showed bilateral lower lobe infiltrates. Urinary antigen assay for Legionella pneumophilia serogroup 1 was positive. Patient was started on intravenous moxifloxacin. On day 5 the patient was discharged home and continued oral moxifloxacin for two weeks. After the two weeks, his respiratory symptoms, gait ataxia and dysarthria resolved. We report the first case of Legionnaires' disease with cerebellar dysfunction and seventh nerve palsy. Legionnaires' disease should be considered in patients with any neurological symptoms in the setting of pneumonia. Failure to recognize and treat the infection may lead to poor outcomes.

Etiology of Community‐Acquired Pneumonia: Increased Microbiological Yield with New Diagnostic Methods

BackgroundThe microbial etiology of community-acquired pneumonia (CAP) is still not well characterized. During the past few years, polymerase chain reaction (PCR)-based methods have been developed for many pathogens causing respiratory tract infections. The aim of this study was to determine the etiology of CAP among adults—especially the occurrence of mixed infections among patients with CAP—by implementing a new diagnostic PCR platform combined with conventional methods.MethodsAdults admitted to Karolinska University Hospital were studied prospectively during a 12-month period. Microbiological testing methods included culture from blood, sputum, and nasopharyngeal secretion samples; sputum samples analyzed by real-time quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed by use of PCR; serological testing for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and viruses common in the respiratory tract; and urine antigen assays for detection of pneumococcal and Legionella pneumophila antigens.ResultsA microbial etiology could be identified for 67% of the patients (n = 124). For patients with complete sampling, a microbiological agent was identified for 89% of the cases. The most frequently detected pathogens were S. pneumoniae (70 patients [38]) and respiratory virus (53 patients [29]). Two or more pathogens were present in 43 (35%) of 124 cases with a determined etiology.ConclusionsBy supplementing traditional diagnostic methods with new PCR-based methods, a high microbial yield was achieved. This was especially evident for patients with complete sampling. Mixed infections were frequent (most commonly S. pneumoniae together with a respiratory virus).

Purulent Pericarditis due to Streptococcus pneumoniae Diagnosed by Pneumococcal Urinary Antigen Assay and 16S rDNA Sequence of the Pericardial Fluid

A 57-year old woman was admitted to our hospital with massive pericardial fluid. Culture of the pericardial fluid was negative, however, Binax NOW Streptococcus pneumoniae urinary antigen test was positive in pericardial fluid. 16S rDNA sequencing and PCR for lyt(A) gene of the pericardial fluid sample confirmed the microbiological diagnosis of S. pneumoniae. The patient was treated with surgical drainage and continuous intravenous infusion of penicillin G and its concentration in the serum and pericardial effusion was monitored. Incorporation of molecular methods such as antigen testing and nucleic acid sequencing would benefit the management of infectious diseases especially in culture negative cases.

Systematic Review and Metaanalysis: Urinary Antigen Tests for Legionellosis

Urinary antigen assays offer simplicity and rapidity in diagnosing Legionnaires' disease, though studies report a range of sensitivities. We conducted a systematic review to assess the test characteristics of Legionella urinary antigen.We searched Medline, Excerpta Medica Database, and bibliographies of retrieved articles. English-language studies were used and included if the absolute number of true-positive, false-negative, true-negative, and false-positive observations were available, and the "gold standards" were described clearly. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Quality Assessment for Diagnostic Accuracy Studies (QUADAS). Sensitivities and specificities were pooled using a random-effects model weighted with the inverse of the SE calculated through the Wald method.Fifty articles were retrieved for detailed evaluation, and 30 met the inclusion criteria. All but two studies focused on serotype 1 Legionella. Forty assays were reported using six different methodologies, whereas 26 assays used commercial tests, and 14 assays used in-house tests. Study quality was generally low, with average QUADAS scores of 4.4 of a total of 14 points (range, 1 to 9 points). The pooled sensitivity was 0.74 (95% CI, 0.68 to 0.81), and the specificity was 0.991 (95% CI, 0.984 to 0.997). Higher quality studies had lower sensitivity, and there was evidence of publication bias.Legionella urinary antigen for serotype 1 appears to have excellent specificity, though modest sensitivity. However, the poor quality of the included studies and the presence of publication bias suggest an overestimation of test performance. High-quality studies are needed.

Severe Legionnaires' Disease Successfully Treated Using a Combination of Fluoroquinolone, Erythromycin, Corticosteroid, and Sivelestat

The patient was a 67-year-old man with diabetes mellitus who had been to a hot spring spa a few days before his admission. The diagnosis of Legionella pneumonia was made using a urinary antigen assay. Intravenous pazufloxacin and oral clarithromycin were started. However, despite these treatments, he developed acute respiratory distress syndrome (ARDS). He was administered the combination of intravenous pazufloxacin and erythromycin, corticosteroid, and sivelestat for two weeks. Then he was successfully recovered. The outcome suggests that treatment with corticosteroid and sivelestat, in addition to a combination of appropriate anti-Legionella antibiotics, should be considered for patients with severe Legionella pneumonia with ARDS.

施設内発症肺炎における肺炎球菌性肺炎の重要性

To clarify the clinical significance of Pneumococcal pneumonia in nursing-home-acquired pneumonia, we examined the positive disease rate of using sputum cultures and the Binax NOW Streptococcus pneumoniae urinary antigen assay in 154 nursing-home patients with pneumonia. These included 54 males and 100 females with a mean age of 86.2 years. Bacteriological findings for sputum culture in 130 patients showed Streptococcus pneumoniae to be cultured in 11 cases (8%). In 72 in whom the Streptococcus pneumoniae-urinary antigen test (Binax NOW) was done, the urinary-antigen-positive rate (26/72 ; 36%) was higher than the culture positive rate for S. pneumoniae. Both examinations were done in 64 patients, among whom 5 in whom S. pneumoniae was cultured also had positive results for the urinary antigen test. Almost half of those undergoing percutaneous endoscopic gastroscopy (PEG) tube nutrition had positive results for the urinary antigen test, but not all such patients had positive cultures for S. pneumoniae. Although the culture-positive rate for S. pneumoniae in sputum was low, we concluded that S. pneumoniae was frequently linked to nursing-home-acquired pneumonia, especially in "total-care" patients.

Systemic Histoplasmosis

To our knowledge, an institutional review of systemic histoplasmosis has not been conducted in the United States since the major outbreaks in Indianapolis in 1978-4982. We conducted a retrospective review of all patients with systemic histoplasmosis diagnosed at Mayo Clinic over a 15-year period. The case definitions employed were based on an international consensus statement by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/IFICG) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG). One hundred eleven patients with systemic histoplasmosis were identified between January 1, 1991, and December 31, 2005. Of these, 78 patients had disseminated histoplasmosis and 55 patients had Histoplasma capsulatum fungemia. The mean age of patients was 55 years, 66% were male, and 98% were white. Fifty-nine percent of patients were immunocompromised. Fever was the most frequently reported symptom (63%), followed by respiratory complaints (43%) and weight loss (37%). The peripheral white blood cell count was <3000 cells/mm in 28%, hemoglobin was <10 g/dL in 29%, and platelet count was <150,000 cells/mm in 41% of patients. Liver enzymes were elevated (alanine aminotransferase >60 U/L in 39%, aspartate aminotransferase >60 U/L in 27%), alkaline phosphatase was >200 U/L in 55%, and albumin was <3.5 g/dL in 70%. Serologic and histopathologic examinations were each positive in 75% of cases, Histoplasma urine antigen screening was positive in 80%, and H. capsulatum was culture positive in 84%. Forty-seven percent of patients were sequentially treated with an amphotericin B-containing product followed by itraconazole, 31% received itraconazole alone, and 7% received an amphotericin B-containing product only. Another 13% of patients did not receive antifungal treatment, and the remaining 2% did not have treatment data available. Sixty percent of patients required hospitalization, and in hospital mortality was 6% with a median survival time of 61 days. The relapse rate was 9%, with a median relapse-free survival of 857 days. Systemic histoplasmosis should be suspected in patients who have lived in endemic areas with fever, bone marrow suppression, and elevated hepatic enzymes, particularly if they are immunocompromised. Evaluation including a combination of Histoplasma serologic screening, urine antigen assay, and fungal culture will secure the diagnosis in most cases.

Contribution of a Pleural Antigen Assay (Binax NOW) to the Diagnosis of Pneumococcal Pneumonia

To determine whether the detection of pneumococcal antigen in pleural fluid augments conventional microbiological methods used for the etiologic diagnosis of pneumonia. In this retrospective study, a rapid immunochromatographic test (ICT) [NOW Streptococcus pneumoniae assay; Binax; Scarborough, ME] was performed on pleural fluid samples from 34 patients with pneumonia due to S pneumoniae, 89 patients with effusions of nonpneumococcal origin, and 17 patients with pneumonia of unknown etiology. Data on blood cultures, pleural fluid cultures, and urinary antigen tests were recorded. The ICT test result was positive in 24 of 34 patients (70.6%) with pneumococcal pneumonia and negative in 83 of 89 patients (93.3%) without pneumococcal pneumonia. The sensitivity of the pleural ICT test was higher than that obtained for blood (37.5%) and pleural fluid cultures (32.3%), but lower than the detection of pneumococcal antigen in urine samples (82.1%). However, three patients with pneumococcal pneumonia and a negative ICT urine test result had a positive pleural fluid antigen detection result test. Previous antibiotic exposure did not influence pneumococcal antigen detection in either pleural fluid or urine specimens. Six additional patients with empyema due to anaerobes (three patients), Streptococcus viridans (two patients), and Enterococcus faecalis (one patient) had false-positive pleural ICT test results. Finally, the ICT assay finding was also positive in 5 of 17 patients (29.4%) with pneumonia without a definite microbiological cause. The ICT test performed on pleural fluid samples augments the standard diagnostic methods of blood and pleural fluid cultures, even in the case of prior antibiotic therapy, and enhances the ICT urinary antigen assay.

Intravenous Ciprofloxacin versus Erythromycin in the Treatment of Legionella Pneumonia

Erythromycin (EM) and rifampicin (RFP) have mainly been used to treat patients with Legionella pneumonia. Since intravenous ciprofloxacin (CPFX) became available in Japan from 2000, many reports have been published detailing successful treatment of Legionella pneumonia with CPFX. In this study, we compared the evolution of patients with Legionella pneumonia treated with CPFX to those treated with EM. The study included nine patients treated with CPFX and eighteen patients treated with EM. Diagnosis of these patients was made by culture, PCR, urinary antigen assay or a serological method. A comparison was made of the patients' characteristics, severity of pneumonia, efficacy of each agent and the clinical course. No significant differences were observed between the two groups, in regard to age, gender, underlying disease or severity of pneumonia. In addition, the period of time from onset of the disease until appropriate therapy did not differ significantly between the two groups. In the CPFX group, all of the patients were cured and in the EM group 16 out of the 18 patients were cured. Although there were no significant differences, the time to apyrexia, normalization of leukocytosis and a 50% decrease in C-reactive protein (CRP) occurred within a relatively shorter time frame in the CPFX group than in the EM group (3.5 versus 4 days, 4 versus 5.2 days, and 2.9 versus 10.3 days, respectively). And, the duration of antibiotic treatment in the CPFX group was significantly shorter than in the EM group. CPFX was as effective as erythromycin in the treatment of Legionella pneumonia. The effects of treatment may appear relatively earlier and the duration of treatment was significantly shorter in patients treated with CPFX therapy than with EM therapy.

A Large, Travel-Associated Outbreak of Legionellosis among Hotel Guests: Utility of the Urine Antigen Assay in Confirming Pontiac Fever

During March 2004, a large outbreak of legionnaires disease and Pontiac fever occurred among hotel guests in Oklahoma. An investigation was conducted to identify the source and evaluate the utility of the Legionella urine antigen assay and serologic testing for the identification of Pontiac fever. A retrospective cohort investigation of hotel guests and employees and an environmental evaluation were performed. Participants were interviewed, and clinical specimens were collected from consenting individuals. Six cases of legionnaires disease and 101 cases of Pontiac fever were identified. Exposure to the indoor pool and hot tub area was associated with legionellosis (relative risk, 4.4; 95% confidence interval, 2.8-6.9). Specimens from the pool and hot tub tested positive for Legionella pneumophila serogroup 1 by polymerase chain reaction. For Pontiac fever, the sensitivity and positive predictive value were 35.7% and 100%, respectively, for the urine antigen assay, and 46.4% and 90%, respectively, for serologic testing. The specificity and negative predictive value were 100% and 47.8%, respectively, for the urine antigen assay, and 89.3% and 45.5%, respectively, for serologic testing. Urine antigen testing, with or without serologic testing, can be used to confirm outbreak-associated cases of Pontiac fever caused by L. pneumophila serogroup 1.

Sporadic and epidemic community legionellosis: two faces of the same illness

The present study compares the risk factors, presentation and outcome of community-acquired Legionella pneumophila pneumonia in 138 sporadic-case patients (1994-2004) and 113 outbreak-case patients (2002) treated in two hospitals in Catalonia (Spain) since urinary antigen assays were adopted. Univariate and multivariate analysis were performed to compare epidemiological and clinical features, blood chemistry values, radiological findings and outcome of sporadic and epidemic legionnaires' disease. Univariate analysis showed that male sex, chronic lung disease, HIV infection and immunosuppressive therapy prevailed in sporadic cases. Presentation with respiratory symptoms, confusion and blood chemistry alterations, such as hyponatraemia, aspartate aminotransferase and blood urea nitrogen elevation, and partial pressure of oxygen P(O)(2) <7.98 KPa (60 mmHg) were also more frequent in sporadic cases, while headache prevailed in outbreak cases. Sporadic cases had a greater delay in treatment, were more severe and had a worse outcome than epidemic cases. Multivariate analysis showed significant differences in sex, chronic lung disease, HIV infection and headache. The clinical and outcome differences between the two groups may be explained by the detection of milder forms of legionnaires' disease, the earlier treatment and the lower severity of underlying disease in the outbreak cases.

Evaluation of the Binax NOW Streptococcus pneumoniae urinary antigen assay in intensive care patients hospitalized for pneumonia

To evaluate the diagnostic performance of Binax Now S. pneumoniae urinary antigen rapid immunochromatographic membrane test (ICT) for patients with suspicion of community-acquired pneumonia hospitalized in intensive care and to assess the impact of prior antibiotics on its diagnostic performance. Retrospective study in a medicosurgical ICU in a 700-bed general hospital. Charts of patients with ICT performed (result blinded) were reviewed between May 2002 and July 2004. ICT has been performed in 140 of the 1,006 patients hospitalized in the unit; two-thirds had received antibiotics prior to admission. Diagnosis of pneumonia was made according to usual criteria. All patients had at least one microbiological test. Pneumonia diagnosis confirmed in 108 patients including 32 pneumococcal. ICT was positive in 23 of 32 patients with pneumococcal pneumonia, in 11 of 108 without, and in none of the 32 patients without pneumonia, resulting in sensitivity, specificity, and positive and negative predictive values of, respectively: 72%, 90%, 68% and 92%. Positive likelihood ratios were comparable among patients with or without prior antibiotics (respectively 6 and 12 for 7 in the overall population). This first clinical evaluation of ICT in intensive care patients hospitalized for suspicion of community-acquired pneumonia, demonstrated performance in accordance with published data even in the case of prior antibiotics. Its clinical interest and impact on antibiotics policy remain to be refined.

Comparison of three Legionella urinary antigen assays during an outbreak of legionellosis in Belgium

During an outbreak of legionellosis in Belgium, urine samples of 32 legionellosis patients were tested with three Legionella urinary antigen assays: the Biotest enzyme immunoassay (EIA) kit, the Binax EIA kit and the Binax NOW Immunochromatographic Test kit. The three tests were concomitantly compared. The test sensitivities on the first urine samples were 65.6 % for the Biotest EIA, 50.0 % for the Binax EIA and 56.3 % for the Binax NOW. Testing of a second urine sample increased the sensitivities to 71.9 %, 59.4 % and 65.6 %, respectively. The differences were not statistically significant. In outbreak settings, testing second samples from patients presenting with symptoms but initially testing negative and/or concentrating urine samples for testing might be valuable additions to the urinary antigen test to increase the sensitivities of the tests.

Fluoroquinolones vs Macrolides in the Treatment of Legionnaires Disease

Erythromycin has been the treatment of choice for Legionnaires disease (LD). However, treatment failure and experimental evidence of its bacteriostatic effect have led to evaluation of new drugs such as fluoroquinolones. This study compared the evolution of patients with LD treated with macrolides and fluoroquinolones. A prospective observational study was performed, and 130 patients from three centers were included. Diagnoses were made using Legionella urinary antigen assay in all patients. Patients receiving any antibiotic > 36 h before starting the study therapy were excluded. Group 1 included 76 patients who received macrolides (33 patients with erythromycin and 43 patients with clarithromycin), and group 2 included 54 patients treated with fluoroquinolones (50 patients with levofloxacin and 4 patients with ofloxacin). No significant differences were seen between the two groups regarding age, sex, smoking, alcohol intake, underlying diseases, or community/hospital acquisition. The time from onset of LD symptoms until the initiation of antibiotic treatment was 78.5 h and 92.7 h in groups 1 and 2, respectively (p = 0.1). Time to apyrexia was significantly longer in the macrolide group (77.1 h vs 48 h for groups 1 and 2, respectively; p = 0.000). There were no differences according to radiology, clinical complications, or mortality. Nevertheless, a trend to a longer hospital stay was observed in the macrolide group (9.9 days vs 7.6 days in groups 1 and 2, respectively; p = 0.09). Fluoroquinolones were as effective as erythromycin in the treatment of LD. It is of note that time to apyrexia was significantly shorter and hospital stay tended to be shorter in patients receiving fluoroquinolones.

Bronchoalveolar lavage findings in severe community-acquired pneumonia due to Legionella pneumophila serogroup 1

Background: No specific data are available in the literature on the bronchoalveolar lavage (BAL) findings of Legionella pneumophila pneumonia. We report on the cytological and immunophenotypical BAL data of three immunocompetent patients with severe community-acquired pneumonia due to L. pneumophila serogroup 1. Methods: Retrospective chart review. The microbiologial diagnosis was obtained by BAL culture or/and urinary antigen assay. Results: All patients presented with high-grade fever, bilateral chest infiltrates and severe respiratory failure requiring ventilatory support. The cytological BAL pattern at presentation showed in all patients the association of a marked neutrophilia with a variable but remarkable percentage of lymphoblasts. Increased levels of activated T-lymphocytes (both HLA-DR+ and CD25+ cells) and, in 2 out of 3 patients, of T-cells bearing the γ/ δ T-cell receptor were the main immunophenotypical findings on flow cytometric analysis. Conclusions: We suggest that the association of lymphoblasts with a marked neutrophilia in BAL fluid of patients with a clinical-radiological setting compatible with acute pneumonia should suggest L. pneumophila as a possible etiologic agent.

Clinical utility of urinary antigen detection for diagnosis of community-acquired, travel-associated, and nosocomial legionnaires' disease.

The clinical utility of Legionella urinary antigen assays for the diagnosis of Legionnaires' disease was assessed by using samples from 317 culture-proven cases. The sensitivities of the Binax enzyme immunoassay (EIA) and Biotest EIA were found to be 93.7 and 94.4% for travel-associated infection and 86.5 and 76.0% for community-acquired infection but only 44.2 and 45.7% for nosocomially acquired infection, respectively.