Evaluation of a rapid immunochromatographic ODK0501 assay for detecting Streptococcus pneumoniae antigens in the sputum of pneumonia patients with positive S. pneumoniae urinary antigens.

BACKGROUND: A novel, rapid and noninvasive test (ODK0501, RAPIRUN(®)Streptococcus pneumoniae) uses polyclonal antibodies to detect C polysaccharide of S. pneumoniae derived from sputum samples using an immunochromatographic assay. We evaluated its usefulness in Japanese patients with pneumonia who exhibited positive urinary antigen tests for S. pneumoniae (BinaxNOW(®)S. pneumoniae). PATIENTS AND METHODS: Forty adult patients with pneumonia treated between May 2011 and August 2013 were enrolled. Bacterial cultures, Gram staining and ODK0501 assays of sputum as well as urinary antigen tests for S. pneumoniae using urine samples obtained from the same patients were performed upon admission, the fourth day after starting antimicrobial treatment and at the end of the antimicrobial treatment. RESULTS: Twenty-seven of the 40 patients were positive for ODK0501, while a negative result for ODK0501 was associated with low-quality sputum samples according to the Geckler classification of sputum. The sensitivity and specificity of the ODK0501 assay in the 40 patients were 90.9% and 61.1%, respectively, based on the culture results. The results obtained with this kit were more favorable than those observed on Gram staining. The ODK0501 assay also showed a rapid reaction to the disappearance of S. pneumoniae in the sputum samples, while approximately 80% of the patients exhibited persistent positive results on the urinary antigen detection tests at the end of treatment. CONCLUSIONS: The ODK0501 test is a noninvasive, rapid and accurate tool for diagnosing respiratory infections caused by S. pneumoniae, although good quality sputum must be obtained prior to adequate treatment with antibiotics.

Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy.

BACKGROUND: Although the reduction in case-fatality rate recently observed among patients with Legionella pneumonia has been largely attributed to the progressive utilization of urine antigen testing, other factors, such as changes in empirical antibiotic therapy, may also have contributed. We have analyzed more-recent outcomes of Legionella pneumonia in an institution where urine antigen testing was reflexly performed in cases of community-acquired pneumonia without an etiological diagnosis. METHODS: From a prospective series of 1934 consecutive cases of community-acquired pneumonia in nonimmunocompromised adults, 139 cases of Legionella pneumophila pneumonia were selected for observational review. Legionella cases were analyzed for outcome with respect to antibiotic treatment, mortality, complications, length of stay, time to defervescence, and stability. RESULTS: The early case-fatality rate was 2.9% (4 of 139 patients), and the overall case-fatality rate was 5% (7 of 139 patients). One hundred twenty patients (86.3%) received an appropriate initial therapy, which included macrolides (i.e., erythromycin or clarithromycin) in 80 patients and levofloxacin in 40. Levofloxacin progressively replaced macrolides as the initial therapy during the study period. Compared with patients who received macrolides, patients who received levofloxacin had a faster time to defervescence (2.0 vs. 4.5 days; P<.001) and to clinical stability (3 vs. 5 days; P=.002). No differences were found regarding the development of complications (25% vs. 25%; P=.906) and case-fatality rate (2.5% vs. 5%; P=.518). The median length of hospital stay was 8 days in patients treated with levofloxacin and 10 days in those who received macrolides (P=.014). CONCLUSIONS: Legionella pneumonia is still associated with significant complications in hospitalized patients, but recent mortality is substantially lower than that found in earlier series. Levofloxacin may produce a faster clinical response than older macrolides, allowing for shorter hospital stay.

Impact of a clinical decision model for febrile children at risk for serious bacterial infections at the emergency department: a randomized controlled trial.

OBJECTIVES: To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED). METHODS: Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n = 219) or the control group (usual care; n = 220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for "pneumonia" and "other SBI". Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses' compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs. RESULTS: The decision model had good discriminative ability for both pneumonia (n = 33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n = 22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value < 0.05) and more urine-dipstick testing (71% vs. 61%, p-value < 0.05). CONCLUSIONS: In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing. TRIAL REGISTRATION: Nederlands Trial Register NTR2381.

[Urine antigen testing: Indication and contribution to the treatment of community-acquired pneumonia]. / Antigénuries: indications de prescription et apports thérapeutiques dans les pneumonies aiguës communautaires.

Urinary antigen tests are quick and simple tests helping to provide an etiological diagnosis in community-acquired pneumonia. However, their prescription is sometimes excessive and performed in unjustified situations. The therapeutic benefit is limited. Indeed, studies show that appropriate antibiotic therapy based on the result of urinary antigen tests does not improve the cost and the patient survival compared to empirical antibiotic therapy. One must be careful before antibiotic therapy reduction based on the sole negative result of urinary antigen test. Legionella urinary antigen test is the most commonly method used for the diagnosis of legionellosis but must be prescribed in a specific clinical context. Streptococcus pneumoniae urinary antigen test is especially interesting in the epidemiological surveillance of pneumococcal community-acquired pneumonia.

[Etiology of community-acquired pneumonia in ambulatory patients. Usefulness of a diagnostic investigation protocol using detection of Streptococcus pneumoniae and Legionella pneumophila antigens in urine samples]. / Etiología de la neumonía adquirida en la comunidad tratada ambulatoriamente. Utilidad de un protocolo diagnóstico con pruebas microbiológicas convencionales y detección de antígenos de Streptococcus pneumoniae y Legionella pneumophila en orina.

BACKGROUND: To determine the etiology of community-acquired pneumonia (CAP) in ambulatory patients and to assess the efficiency of a diagnostic protocol by using tests to detect bacterial antigens in urine samples. PATIENTS AND METHOD: One-year prospective study that included blood and sputum cultures, serologic studies, and detection of Legionella pneumophila and Streptococcus pneumoniae urinary antigens. RESULTS: 49 patients were recruited and an etiological diagnosis was attained in 34 (69%). Microorganisms most frequently isolated were S. pneumoniae (12 cases), Mycoplasma pneumoniae (7), Haemophilus influenzae (4), respiratory viruses (4) and Coxiella burnetii (3 cases). CONCLUSIONS: By means of a non-invasive protocol with urinary antigen tests, a microbial etiology can be established in two thirds of patients with mild CAP. S. pneumoniae is the main cause of mild CAP.

Atypical pathogens as etiologic agents in hospitalized patients with community-acquired pneumonia in Korea: a prospective multi-center study.

Local epidemiologic data on the etiologies of patients hospitalized with community-acquired pneumonia (CAP) is needed to develop guidelines for clinical practice. This study was conducted prospectively to determine the proportion of atypical bacterial pathogens in adults patients hospitalized with CAP in Korea between October 2001 and December 2002. Microbiological diagnosis was determined by serology for antibodies to Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. Nucleic acid of M. pneumoniae and C. pneumoniae in respiratory samples and Legionella antigen in urine samples were detected. The study population consisted of 126 patients (71 males, 55 females), averaging 54.6 yr (SD+/-17.8), whose paired sera were available. An etiologic diagnosis for atypical pathogens was made in 18 patients (14.3%): C. pneumoniae 9 (7.1%), M. pneumoniae 8 (6.3%), and L. pneumophila 3 patients (2.4%). Streptococcus preumoniae and other typical pathogens were isolated from 36 patients (28.6%). Of 126 patients, 16 (12.7%) were admitted to intensive care unit and atypical pathogens were identified in 5 patients (31.3%). Initial clinical features of patients with pneumonia due to atypical, typical or undetermined pathogens were indistinguishable. We conclude that atypical pathogens should be seriously considered in hospitalized patients with CAP, when initiating empiric treatment in Korea.

Comparison of two urinary antigen tests for establishment of pneumococcal etiology of adult community-acquired pneumonia.

The Binax NOW immunochromatographic test (ICT) detecting the pneumococcal C polysaccharide and a serotype-specific latex agglutination (LA) test detecting 23 pneumococcal capsular antigens were evaluated for establishing pneumococcal etiology in community-acquired pneumonia (CAP) by use of nonconcentrated urine. ICT was considered to be strongly positive for result lines at least as intense as the control line and weakly positive for less intense result lines. When 215 adult CAP patients were tested, strong ICT, weak ICT, and LA positivity were found in 28, 24, and 16 patients, respectively; of these patients, 13 (46%), 6 (25%), and 13 (81%), respectively, had pneumococcal bacteremia and 27 (96%), 17 (71%), and 15 (94%), respectively, had Streptococcus pneumoniae isolated from blood, sputum, and/or nasopharynx. Among 108 controls tested, 2 (1.9%) were weakly ICT positive. When weak positivity was considered negative, the sensitivity of ICT decreased from 79% (19 of 24) to 54% (13 of 24), while the specificity increased from 83% (158 of 191) to 92% (176 of 191); no controls were false positive. The sensitivity and specificity of LA were 54% (13 of 24) and 98% (188 of 191), respectively. Eight of nine LA serotypes corresponded to culture serotypes. In conclusion, using nonconcentrated urine and dividing ICT-positive results into strongly and weakly positive results is a suitable way of performing ICT. While weak ICT positivity should be interpreted with caution, strong ICT positivity and LA positivity should be considered supportive of pneumococcal etiology in adult CAP. As such, these assays might have implications for antibiotic use in CAP. LA has promising potential for pneumococcal serotyping, although further evaluation is required.

Use of the polymerase chain reaction to detect Legionella DNA in urine and serum samples from patients with pneumonia.

Legionella pneumonia can be difficult to diagnose. Existing laboratory tests for detecting Legionella species lack sensitivity or provide only a retrospective diagnosis. We used the polymerase chain reaction (PCR) with primers that amplify a 104-base pair segment of the coding region of the 5S tRNA gene to detect Legionella DNA in urine and serum samples from patients with pneumonia. Stored urine and serum samples from patients enrolled in two prospective studies of pneumonia were tested. Legionella DNA was detected in urine and/or serum samples from 18 (64%) of 28 patients with legionella pneumonia diagnosed by conventional tests, but it was not detected in urine or serum samples from 24 patients with pneumonia due to other organisms. The sensitivity of PCR improved to 73% if testing was restricted to samples taken within 4 days of the onset of symptoms. Detection of Legionella DNA in urine and serum promises to be a valuable tool for the rapid diagnosis of legionella pneumonia.