Age-stratified burden of pneumococcal community acquired pneumonia in hospitalised Canadian adults from 2010 to 2015.

BACKGROUND: In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age. METHODS: Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16-49, 50-64, ≥65 and ≥50 years). RESULTS: Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively. CONCLUSIONS: Adults hospitalised with pCAP in the age cohort of 50-64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

Usefulness of Early C-Reactive Protein Kinetics in Response and Prognostic Assessment in Infected Critically Ill Patients: An Observational Retrospective Study.

INTRODUCTION: The ideal biomarker to assess response and prognostic assessment in the infected critically ill patient is still not available. The aims of our study were to analyze the association between early C-reactive protein kinetics and duration and appropriateness of antibiotic therapy and its usefulness in predicting mortality in infected critically ill patients. MATERIAL AND METHODS: We have carried out an observational retrospective study in a cohort of 60 patients with community-acquired pneumonia, aspiration pneumonia and bacteremia at an intensive care unit. We have collected C-reactive protein consecutive serum levels for eight days as well as duration and appropriateness of initial antibiotic therapy. C-reactive protein kinetic groups were defined based on the levels at days 0, 4 and 7. With a follow-up of one year, we have evaluated mortality at different time-points. RESULTS: We have obtained three different C-reactive protein kinetic groups from the sample: fast response, delayed but fast response and delayed and slow response. We did not find statistically significant associations between C-reactive protein kinetics and early (intensive care unit, hospital and 28-days) or late (six months and one year) mortality and antibiotic therapy duration (p > 0.05). Although there were no statistically significant differences between the appropriateness of antibiotic therapy and the defined groups (p = 0.265), no patient with inappropriate antibiotic therapy presented a fast response pattern. DISCUSSION: Several studies suggest the importance of this protein in infection. CONCLUSION: Early C-reactive protein kinetics is not associated with response and prognostic assessment in infected critically ill patients. Nevertheless, a fast response pattern tends to exclude initial inappropriate antibiotic therapy.

Introdução: O biomarcador ideal capaz de avaliar a resposta e prognóstico no doente crítico infetado ainda não está disponível. Os objetivos do nosso estudo foram avaliar a relação da cinética precoce da proteína C-reativa com a duração e apropriação da terapêutica antibiótica e a sua utilidade na predição de mortalidade. Material e Métodos: Realizámos um estudo retrospetivo observacional numa coorte de 60 doentes com pneumonia adquirida na comunidade, pneumonia de aspiração e bacteremia numa unidade de cuidados intensivos. Colhemos níveis séricos de proteína C-reativa durante oito dias e a duração e apropriação da terapêutica antibiótica inicial. Definimos grupos de cinética de proteína C-reativa com base nos níveis dos dias 0, 4 e 7. Durante um ano de seguimento, analisámos a mortalidade em diferentes momentos. Resultados: Da amostra obtivemos três grupos de cinética de proteína C-reativa: resposta rápida, resposta atrasada mas rápida e resposta atrasada e lenta. Não observamos associação estatisticamente significativa entre a cinética da proteína C-reativa com a mortalidade precoce (unidade de cuidados intensivos, hospital e aos 28 dias) ou tardia (seis meses e um ano) e duração da terapêutica antibiótica (p > 0,05). Embora não existam diferenças estatisticamente significativas entre a apropriação da terapêutica antibiótica e os grupos definidos (p = 0,265), nenhum doente com terapêutica antibiótica inapropriada apresentou um padrão de resposta rápida. Discussão: Vários estudos sugerem a importância desta proteína na infeção. Conclusão: A cinética precoce da proteína C-reativa não está associada com a avaliação da resposta e prognóstico no doente crítico infectado. Porém, um padrão de resposta rápida tende a excluir terapêutica antibiótica inicial inapropriada.

Comprehensive analysis of prognostic factors in hospitalized patients with pneumonia occurring outside hospital: Serum albumin is not less important than pneumonia severity assessment scale.

PURPOSE: This study aimed to elucidate factors related to 30-day mortality of pneumonia occurring outside hospital by comprehensively analyzing data considered relevant to prognosis. METHODS: Data considered relevant to prognosis were retrospectively examined from clinical charts and chest X-ray images of all patients with pneumonia occurring outside hospital admitted to our hospital from 2010 to 2016. The primary outcome was 30-day mortality. RESULTS: Data were collected from 534 patients (317 community-acquired pneumonia and 217 nursing- and healthcare associated pneumonia patients; 338 men (63.3%); mean age, 76.2 years-old). Eighty-three patients (9.9%) died from pneumonia within 30 days from the date of admission. The numbers of patients with pneumonia severity index (PSI) classes of I/II/III/IV/V and age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scores of 0/1/2/3/4/5 were 29/66/127/229/83, and 71/107/187/132/30/7, respectively. Mean (standard deviation) body mass index (BMI), serum albumin, blood procalcitonin, white blood cell and C-reactive protein were 20.00 (4.12) kg/m2, 3.16 (0.60) g/dL, 3.69 (13.15) ng/mL, 11559.4 (5656.9)/mm3, and 10.92 (8.75) mg/dL, respectively. Chest X-ray images from 152 patients exhibited a pneumonia shadow over a quarter of total lung field. Logistic regression analysis revealed that PSI class or A-DROP score, BMI, serum albumin, and extent of pneumonia shadow were related to 30-day mortality. Receiver operating characteristics curve analysis revealed that serum albumin was superior to PSI class or A-DROP score for predicting 30-day mortality. CONCLUSION: Serum albumin is not less important than PSI class or A-DROP score for predicting 30-day mortality in hospitalized patients with pneumonia occurring outside hospital.

Association of hypercapnia on admission with increased length of hospital stay and severity in patients admitted with community-acquired pneumonia: a prospective observational study from Pakistan.

OBJECTIVE: To determine whether the presence of hypercapnia on admission in adult patients admitted to a university-based hospital in Karachi, Pakistan with community-acquired pneumonia (CAP) correlates with an increased length of hospital stay and severity compared with no hypercapnia on admission. STUDY DESIGN: A prospective observational study. SETTINGS: Tertiary care hospital in Karachi, Pakistan. METHODS: Patients who met the inclusion criteria were enrolled in the study. The severity of pneumonia was assessed by CURB-65 and PSI scores. An arterial blood gas analysis was obtained within 24 hours of admission. Based on arterial PaCO2 levels, patients were divided into three groups: hypocapnic (PaCO2 <35 mm Hg), hypercapnic (PaCO2 >45 mm Hg) and normocapnic (PaCO2 <35-45 mm Hg). OUTCOMES: The primary outcome was the association of hypercapnia on admission with mean length of hospital stay. Secondary outcomes were the need for mechanical ventilation, ICU admission and in-hospital mortality. RESULTS: A total of 295 patients of mean age 60.20±17.0 years (157 (53.22%) men) were enrolled over a 1-year period. Hypocapnia was found in 181 (61.35%) and hypercapnia in 57 (19.32%) patients. Hypercapnic patients had a longer hospital stay (mean 9.27±7.57 days), increased requirement for non-invasive mechanical ventilation (NIMV) on admission (n=45 (78.94%)) and longer mean time to clinical stability (4.39±2.0 days) compared with the other groups. Overall mortality was 41 (13.89%), but there was no statistically significant difference in mortality (p=0.35) and ICU admission (p=0.37) between the three groups. On multivariable analysis, increased length of hospital stay was associated with NIMV use, ICU admission, hypercapnia and normocapnia. CONCLUSION: Hypercapnia on admission is associated with severity of CAP, longer time to clinical stability, increased length of hospital stay and need for NIMV. It should be considered as an important criterion to label the severity of the illness and also a determinant of patients who will require a higher level of hospital care. However, further validation is required.

Assessment of Cytokine and Chemokine Signatures as Potential Biomarkers of Childhood Community-acquired Pneumonia Severity: A Nested Cohort Study in India.

BACKGROUND: Pediatric community-acquired pneumonia (CAP) is a leading cause of childhood mortality in developing countries. In resource-poor settings, pneumonia diagnosis is commonly made clinically, based on World Health Organization guidelines, where breathing difficulty or cough and age-adjusted tachypnea suffice to establish diagnosis. Also, the severity of CAP is generally based on clinical features and existing biomarkers do not reliably correlate to either clinical severity or outcome. Here, we asked whether systemic immune and inflammatory mediators could act as biomarkers predicting CAP severity or outcome. METHODS: Serum from a subset of a CAP cohort (n = 196), enrolled in India, classified according to World Health Organization criteria as having pneumonia or severe pneumonia, was used for simultaneous measurement of 21 systemic cytokines and chemokines. RESULTS: We found significantly higher IL-6, IL-8, IL-13, IFN-γ and lower CCL22 concentrations in patients with severe compared with mild CAP (P values: 0.019, 0.036, 0.006, 0.016 and 0.003, respectively). Based on higher MIP-1α, IL-8, IL-17 or lower CCL22 response pattern at the time of enrolment, children with fatal outcome showed markedly different pattern of inflammatory response compared with children classified with the same disease severity, but with nonfatal outcome (P values: 0.043, 0.017, 0.008 and 0.020, respectively). CONCLUSIONS: Our results suggest a relation between an elevated mixed cytokine response and CAP severity on one hand, and a bias toward uncontrolled neutrophilic inflammation in subjects with fatal outcome on the other. Collectively our findings contribute to increased knowledge on new biomarkers that can potentially predict severity and outcome of childhood CAP in the future.

Severity Assessment and the Immediate and Long-Term Prognosis in Community-Acquired Pneumonia.

Severity assessment is a crucial step in the initial management of patients with community-acquired pneumonia (CAP). While approximately half of patients are at low risk of death and can be safely treated as outpatients, around 20% are at increased risk. While CURB-65 (confusion, respiratory rate, blood pressure, urea) and pneumonia severity index (PSI) scores are equally useful as an adjunct to clinical judgment to identify patients at low risk, the so-called minor American Thoracic Society/Infectious Diseases Society of America criteria are predictive of patients in need of intensified treatment (i.e., mechanical ventilation and/or vasopressor treatment). Such patients represent medical emergencies. In elderly patients, CRB-65 (confusion, respiratory rate, blood pressure, age) is no longer predictive of low risk; instead, poor functional status is the best predictor of death. In addition to scores, assessment of oxygenation and unstable comorbidity, as well as lactate and biomarkers remain important to consider. The added value of combined clinical and biomarker risk stratification strategies should be evaluated in large prospective interventional trials.Survivors of hospitalized CAP have a considerable excess long-term mortality. Risk factors include age, male gender, and nursing home residency, as well as increased PSI and CURB-65 scores. Cardiovascular, pulmonary, renal, and neoplastic comorbidities are prominent causes of long-term mortality. Comorbidities are vulnerable to both the acute and chronic subclinical inflammatory challenge delivered by pulmonary infection and are thereby drivers of mortality. Biomarkers are promising in identifying patients at increased risk of long-term mortality. Future studies should develop consistent strategies of risk stratification and intervention to improve long-term outcomes of patients with CAP.

Valuable hematological indicators for the diagnosis and severity assessment of Chinese children with community-acquired pneumonia: Prealbumin.

Chest X-ray is a "golden standard" for the diagnosis and severity assessment of community-acquired pneumonia (CAP). However, it cannot be used as routine examination of CAP in children. The present study aims to investigate the roles of prealbumin (PA) in CAP in children and further determine the usefulness of PA in diagnosis and severity assessment of CAP in children.This was a retrospective analysis of 174 cases of hospitalized children with CAP. The following indicators were recorded: vital sign, inflammatory indexes, PA, and respiratory pathogens immunoglobulin M antibody test results. A total of 33 healthy children were selected as the control group. The results of laboratory tests between CAP and control groups were compared. CAP group was further divided into mild CAP and severe CAP groups, and vital signs and laboratory examination results of 2 groups were compared.The total positive rate of Mycoplasma pneumoniae in this study was 27.4%, and there was no significant difference in different seasons (P = 0.356). Compared with controls, there was no significant difference between procalcitonin and C-reactive protein in CAP group (P = 0.355, 0.061). The white blood cell count, percentage of neutrophils, neutrophil count, and erythrocyte sedimentation rate in the CAP group were significantly higher than those in control group, and PA was significantly lower than that in the control group (all P < 0.05). In the traditional cutoff value (<170 mg/L), the sensitivity of PA for the diagnosis of CAP was 0.847, which was significant higher than traditional inflammatory indicators. Moreover, it was found that PA was an independent protective factor for CAP in children based on multivariate analysis (odds ratio: 0.974; 95% confidence interval: 0.956-0.993; P = 0.008). PA level in severe CAP group was significantly lower than in mild CAP group (P = 0.001). With a cutoff value of 125 mg/L, the sensitivity and specificity of PA for the severity assessment of CAP were 0.703 and 0.714, respectively.Combined with traditional inflammatory markers, PA may improve the diagnostic efficacy of CAP in children. PA can be used as a reference marker to complement the chest X-rays for severity assessment of children CAP.

Utility of serum procalcitonin and C-reactive protein in severity assessment of community-acquired pneumonia in children.

OBJECTIVES: Although the importance of serum Procalcitonin (PCT) levels at diagnosis is well established in adult Community-Acquired Pneumonia (CAP), its use remains controversial in pediatric CAP. The aim of our study is to investigate the role of PCT and C-Reactive Protein (CRP) in the assessment of pediatric CAP severity defined by the extent of consolidation on chest X-rays and the presence of pleural effusion. In this particular setting, no clinical severity score is available at present and chest X-ray, although important for diagnosis confirmation, is not recommended as routine test. DESIGN AND METHODS: The study involved 119 children admitted to the Department of Pediatric Infectious Disease for radiographically documented CAP aged 1 year to 14 years, without chronic diseases. Baseline PCT, CRP and routine laboratory tests were performed on admission. RESULTS: The median PCT (µg/L) and CRP (mg/L) were 0.11 (0.05­0.58) and 21.3 (4.2­48.1), respectively. PCT showed a good correlation with CRP, neutrophils and WBC (r = 0.538, P < 0.001; r = 0.377, P < 0.001; r = 0.285, P0.002, respectively). CRP, but not PCT, was associated with lobar consolidation (P = 0.007) and pleural effusion (P = 0.002). Logistic regression analysis revealed that only CRP was a predictor of lobar consolidation (OR: 1.078; 95% CI: 1.017­1.143; P = 0.011) and pleural effusion (OR: 1.076; 95% CI: 1.005­1.153; P = 0.036). CONCLUSION: Our findings revealed that PCT is correlated to the main inflammatory markers in children with CAP. CRP, unlike PCT, is able to predict the extent of chest X-ray infiltration and ultimately the severity of the disease confirming its usefulness in the management of pneumonia

Development and Assessment of a Nomogram to Propose the Initial Dosage Regimen of a Meropenem Infusion Based on Serum Creatinine and Age Using a Monte Carlo Simulation.

A conventional nomogram, based on serum creatinine (sCr) and age, was developed in order to determine the correct initial dosage regimen for meropenem (MEPM) infusions in elderly patients with severe community-acquired pneumonia (CAP), using a target minimum inhibitory concentration (MIC) of 2 mg/L. A correlation between age and actual bodyweight (BW) in a development cohort of 44 males and 45 females was performed by linear regression using the least-squares method (male: y=-0.4676x+80.281, R(2)=0.4888; female: y=-0.4373x+77.502, R(2)=0.3194). There were no significant differences between actual BW and the BW (e-BW) estimated using this equation in this cohort (male: e-BW 41.6±3.1 kg, BW 41.7±3.5 kg, p=0.93; female: e-BW 39.5±2.1 kg, BW 39.5±3.7 kg, p=0.20). By integrating these equations using the Monte Carlo simulation method, a dosage regime was calculated which would have an 80% probability of maintaining plasma drug levels above the MIC for more than 40% of the time (>40%TAM), using only the age and sCr of individual patients. This relationship was summarized as a nomogram. The nomogram was validated using an independent validation cohort (n=28) of patients. An optimized dosage regimen could be predicted in 84 patients (94.4%) in the development cohort and 25 patients (89.3%) in the validation cohort. This nomogram may be a useful tool for clinicians and pharmacists in determining an initial MEPM regimen in elderly patients with severe CAP, based only on age and sCr.

A Cost-Effectiveness Analysis of Obtaining Blood Cultures in Children Hospitalized for Community-Acquired Pneumonia.

OBJECTIVE: To determine the clinical utility and cost-effectiveness of universal vs targeted approach to obtaining blood cultures in children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN: We conducted a cost-effectiveness analysis using a decision tree to compare 2 approaches to ordering blood cultures in children hospitalized with CAP: obtaining blood cultures in all children admitted with CAP (universal approach) and obtaining blood cultures in patients identified as high risk for bacteremia (targeted approach). We searched the literature to determine expected proportions of high-risk patients, positive culture rates, and predicted bacteria and susceptibility patterns. Our primary clinical outcome was projected rate of missed bacteremia with associated treatment failure in the targeted approach. Costs per 100 patients and annualized costs on the national level were calculated for each approach. RESULTS: The model predicts that in the targeted approach, there will be 0.07 cases of missed bacteremia with treatment failure per 100 patients, or 133 annually. In the universal approach, 118 blood cultures would need to be drawn to identify 1 patient with bacteremia, in which the result would lead to a meaningful antibiotic change compared with 42 cultures in the targeted approach. The universal approach would cost $5178 per 100 patients or $9,214,238 annually. The targeted approach would cost $1992 per 100 patients or $3,545,460 annually. The laboratory-related cost savings attributed to the targeted approach would be projected to be $5,668,778 annually. CONCLUSIONS: This decision analysis model suggests that a targeted approach to obtaining blood cultures in children hospitalized with CAP may be clinically effective, cost-saving, and reduce unnecessary testing.

Accuracy of PaO2 /FiO2 calculated from SpO2 for severity assessment in ED patients with pneumonia.

BACKGROUND AND OBJECTIVE: Assessment of oxygenation in patients with community-acquired pneumonia is critical for treatment. The accuracy of percutaneous oxygen saturation (SpO2 ) determined by pulse oximetry is uncertain, and it has limited value in patients receiving supplemental oxygen. We hypothesized that calculation of partial arterial oxygen concentration/inspired oxygen faction (PaO2 /FiO2 ) from SpO2 by the Ellis or Rice equations might adequately correlate with PaO2 /FiO2 measured by arterial blood gases. METHODS: We studied 1004 patients with pneumonia in the emergency department with simultaneous measurement of SpO2 and PaO2 from two cohorts from Valencia, Spain and Utah, USA. We compared SpO2 with measured SaO2 , compared the equations' accuracy in calculating PaO2 /FiO2 and determined how often patients would be misclassified at clinically important thresholds. We compared estimated PaO2 /FiO2 to measured PaO2 /FiO2 using the Spearman correlation. RESULTS: Pairwise correlation of SpO2 with SaO2 was moderate (rho = 0.66; P < 0.01). Both equations performed similarly among patients with lower PaO2 /FiO2 ratios. The Ellis equation estimated PaO2 /FiO2 from SpO2 more accurately than the Rice equation in patients with PaO2 /FiO2 ≥200. Simple agreement between calculated and measured P/F was 91% and 92%, respectively. CONCLUSIONS: The Ellis equation was more accurate than the Rice equation for estimating PaO2 /FiO2 , especially at higher levels of P/F ratio. Estimation of PaO2 /FiO2 from SpO2 is accurate enough for initial oxygenation assessment. Ellis and Rice equations could misclassify 20% and 30% of patients, respectively, at higher levels of PaO2 /FiO2 . For patients with abnormal oxygenation falling near thresholds for clinical decision making, arterial blood gas measurement preferably on room air is more accurate.

Endogenous carboxyhemoglobin concentrations in the assessment of severity in patients with community-acquired pneumonia.

INTRODUCTION: Previous studies have shown that carbon monoxide, which is endogenously produced, is increased in community-acquired pneumonia (CAP). However, it has not been studied enough whether severity of pneumonia is correlated with increased carboxyhemoglobin (COHb) concentrations in CAP. The aim of this study was to determine whether endogenous carbon monoxide levels in patients with CAP were higher compared with the control group and, if so, to determine whether COHb concentrations could predict severity in CAP. MATERIALS AND METHODS: Eighty-two patients with CAP were evaluated in this cross-sectional study during a 10-month period. Demographic data, pneumonia severity index and confusion, uremia, rate respiratory, pressure blood, age>65 (CURB-65) scores, hospital admission or discharge decisions, and 30-day hospital mortality rate were recorded. In addition, 83 control subjects were included to study. The COHb concentration was measured in arterial blood sample. RESULTS: The levels of COHb in patients with CAP were 1.70% (minimum-maximum, 0.8-3.2), whereas those in control subjects, 1.40% (minimum-maximum, 0.8-2.9). The higher COHb concentrations in patients with CAP were statistically significant (P < .05). Concentration of COHb correlated with pneumonia severity index (P = .04, r = 0.187); however, it did not correlate with CURB-65 (P = .218, r = 0.112). CONCLUSION: Although COHb concentrations show an increase in patients with pneumonia, it was concluded that this increase did not act as an indicator in diagnosis process or prediction of clinical severity for the physicians.

Assessment of inflammatory markers in patients with community-acquired pneumonia--influence of antimicrobial pre-treatment: results from the German competence network CAPNETZ.

BACKGROUND: There is almost no data about the influence of antimicrobial pre-treatment (APT) on levels of inflammatory markers in community acquired pneumonia (CAP). The aim of this study was to investigate the influence of APT on inflammatory markers in CAP. METHODS: 991 hospitalized patients (64.3±17.6 years, 61% male) with CAP were enrolled. In all patients procalcitonin (PCT), C-reactive protein (CRP), and leukocyte count (WBC) were determined. Patients were followed-up for 28 days for survival. RESULTS: 232 patients (23.4%) had APT, 759 had no APT. Patients without APT had significantly higher levels of PCT and WBC but not of CRP compared to those with APT. In patients without APT, survivors compared to non-survivors had lower values of PCT (0.20 ng/mL; 0.02-169.10 vs. 0.83 ng/mL; 0.04-516.30, p<0.0001), WBC (12.4×10(9)/L; 1.3-49.9 vs. 14.9×10(9)/L; 3.7-34.5, p=0.047) and CRP (107.0mg/mL; 0.3-567.0 vs. 143.5mg/mL; 5.0-589.0, p=0.006). However, in patients with APT, the values of PCT, WBC and CRP were not significantly different in survivors and non-survivors. Cox regression analysis confirmed that PCT, CRP and WBC were predictive for 28 day mortality in patients without APT but not in those with APT. CONCLUSIONS: PCT and WBC but not CRP levels are higher in patients without APT compared to those with APT. PCT, CRP and WBC are predictive for 28 days mortality exclusively in patients without APT. Interpretation of inflammatory parameters has to take into account possible APT.

[Assessment of the contribution of the immunochromatographic pneumococcal urinary antigen test to the etiological diagnosis of pneumonia in hospitalized adults]. / Bilan de la contribution de l'antigénurie pneumocoque par test immunochromatographique au diagnostic étiologique des pneumonies chez l'adulte hospitalisé.

AIM OF THE STUDY: To assess the usefulness and prescription practices of the Binax Now Streptococcus pneumoniae urinary antigen test in hospitalized adults. PATIENTS AND METHODS: The results of the pneumococcal urinary antigen tests (UAT) performed from January 2002 to September 2004 were related to that of microbiological cultures, and in positive patients to radiographic findings and C-reactive protein (CRP) levels. The evolution of the number of prescriptions and positivity rate in 2007 versus 2002-2004 was analyzed. RESULTS: The pneumococcal UAT was positive in 32 of the 278 patients included from 2002 to 2004 (11.5%). Results were concordant with that of microbiological cultures in 90% of the 247 documented cases. Pneumococcal etiology was considered to be definite in 19 patients (isolation of S. pneumoniae from blood, 17 patients; or pleural fluid, two patients), of whom 15 had a positive UAT (sensitivity: 79%); to be probable in 22 patients (positive UAT, 17 patients and/or isolation of S. pneumoniae from respiratory samples, six patients), and was retained in 39 of the 41 patients (positive predictive value: 93.7%). CRP was greater than 100mg/L in 34 of 39 documented patients and lobar alveolar radiographic opacities observed in 25 of 28 documented patients. In 2007, the dramatic increase in the number of UAT prescriptions and the diversification of prescribing units were associated to a decreased positivity rate (8.1%). CONCLUSION: Whereas the pneumococcal UAT clearly increases etiological diagnosis, pneumococcal pneumonia cannot be ruled out if negative. Indications for its use need to be refined to improve the cost-effectiveness of this test.

Pharmacodynamic target attainment potential of azithromycin, clarithromycin, and telithromycin in serum and epithelial lining fluid of community-acquired pneumonia patients with penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae.

OBJECTIVE: To compare the probability of target attainment (PTA) for macrolides and ketolides against penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae in both serum and epithelial lining fluid (ELF) of patients with community-acquired pneumonia (CAP). METHODS: Monte Carlo simulations were used to assess the attainment of the bacterial eradication-linked pharmacodynamic index of the free drug area under the concentration-time curve over 24 hours to minimum inhibitory concentration (fAUC(0-24)/MIC90) by azithromycin, clarithromycin, and telithromycin, at therapeutic doses, against penicillin-susceptible, intermediate, and resistant S. pneumoniae. RESULTS: In serum, azithromycin and clarithromycin were found to have a probability of attaining the recommended fAUC(0-24)/MIC90 ratio of 30 in 50.2% and 74.6%, respectively, of CAP patients with penicillin-intermediate strains, and a probability of 36.9% and 60.7%, respectively, in cases of penicillin-resistant strains. Telithromycin maintained a probability of reaching the fAUC(0-24)/MIC90 ratio of 30 in serum and ELF in 89.1% of CAP patients, regardless of the penicillin resistance of the strain. CONCLUSIONS: Clarithromycin results in a higher PTA than azithromycin in the treatment of penicillin-susceptible S. pneumoniae, but both of these agents exhibit a decreasing efficacy as S. pneumoniae penicillin resistance increases. When compared to clarithromycin and azithromycin, telithromycin maintains higher PTA in CAP patients with penicillin-resistant strains of S. pneumoniae.

Assessment of B-type natriuretic peptide in patients with pneumonia.

The mammalian heart synthesises and secretes B-type natriuretic peptide (BNP), which has potent diuretic, natriuretic and vascular smooth muscle-relaxing effects as well as complex interactions with the hormonal and nervous systems. Recent studies described that BNP was acute phase reactant. In this study, we aimed to evaluate BNP levels in patients with pneumonia. Twenty-one patients with pneumonia and 21 healthy control subjects were enrolled in this study. Their serum levels of BNP were measured in addition to the standard evaluations. Leucocyte count [19.3 (13.2-25.7) 10(6)/ml vs. 9.55 (3.7-13.9) 10(6)/ml, p < 0.001], erythrocyte sedimentation rate [73 (57-81) mm/h vs. 35 (4-55) mm/h, p < 0.001], C-reactive protein (CRP) [127.72 (27-290) mg/l vs. 13.19 (3-41) mg/l, p < 0.001] and BNP [53.1 (17-91) pg/ml vs. 16.24 (1-38) pg/ml, p < 0.001] levels significantly decreased after treatment period. Initial BNP levels were significantly higher than control groups (53.10 +/- 15.07 pg/ml vs. 18.62 +/- 14.05 pg/ml, p < 0.001) and decreased after treatment to the levels comparable with control subjects. BNP levels correlated with CRP levels at admission (r = 0.716, p < 0.001). We have shown that BNP levels show a transient increase in patients with pneumonia and correlate well with CRP.

Blood cultures do not change management in hospitalized patients with community-acquired pneumonia.

OBJECTIVES: To determine if blood cultures identify organisms that are not appropriately treated with initial empiric antibiotics in hospitalized patients with community-acquired pneumonia, and to calculate the costs of blood cultures and cost savings realized by changing to narrower-spectrum antibiotics based on the results. METHODS: This was a retrospective observational study conducted in an urban academic emergency department (ED). Patients with an ED and final diagnosis of community-acquired pneumonia admitted between January 1, 2001, and August 30, 2003, were eligible when the results of at least one set of blood cultures obtained in the ED were available. Exclusion criteria included documented human immunodeficiency virus infection, immunosuppressive illness, chronic renal failure, chronic corticosteroid therapy, documented hospitalization within seven days before ED visit, transfer from another hospital, nursing home residency, and suspected aspiration pneumonia. The cost of blood cultures in all patients was calculated. The cost of the antibiotic regimens administered was compared with narrower-spectrum and less expensive alternatives based on the results. RESULTS: A total of 480 patients were eligible, and 191 were excluded. Thirteen (4.5%) of the 289 enrolled patients had true bacteremia; the organisms isolated were sensitive to the empiric antibiotics initially administered in all 13 cases (100%; 95% confidence interval = 75% to 100%). Streptococcus pneumoniae and Haemophilus influenzae were isolated in 11 and two patients, respectively. The potential savings of changing the antibiotic regimens to narrower-spectrum alternatives was only 170 dollars. CONCLUSIONS: Appropriate empiric antibiotics were administered in all bacteremic patients. Antibiotic regimens were rarely changed based on blood culture results, and the potential savings from changes were minimal.

[C-reactive protein, leukocyte count and ESR in the assessment of severity of community-acquired pneumonia]. / Toplum kökenli pnömonilerin agirliginin degerlendirilmesinde C-reaktif protein, lökosit sayisi ve eritrosit sedimentasyon hizinin yeri.

This study aimed to evaluate the relations between the levels of CRP, leukocyte count and ESR on admission and the severity of pneumonia according to the criteria of Turkish Thoracic Society (TTS) and British Thoracic Society (BTS) CAP guidelines. This study included the adult patients with CAP admitted to our clinic between the years 2003-2005. The history, physical findings, hemogram, ESR, the levels of CRP and the results of other laboratory investigations were obtained from the medical records. The patients were grouped according to BTS and TTS guidelines. The mean age was 47.2 years; 70 patients (75.3%) were male and 23 patients (24.7%) were female. The severity of pneumonia according to BTS criteria was correlated with the levels of CRP and leukocyte count (p= 0.037, p= 0.01, respectively). The severity of pneumonia according to TTS criteria was correlated with the levels of CRP, leukocyte count and ESR (p= 0.000, p= 0.014, p= 0.015, respectively). Among TTS pneumonia groups, there were statistically significant differences between groups 1 and 3; groups 1 and 4; groups 2 and 3 (p= 0.006, p= 0.041, p= 0.05, respectively) for mean CRP levels. The mean levels of CRP (103.2 +/- 76.4 mg/L), leukocyte count (19.8 +/- 9.5 x 10(3)/microL) and ESR (57.2 +/- 26.8 mm/hour) were statistically significantly higher in inpatients than the mean levels of CRP (53.2 +/- 52.8 mg/dL), leukocyte count (14.6 +/- 5.4 x 10(3)/microL) and ESR (43.1 +/- 25.9 mm/hour) in outpatients (p= 0.000, p= 0.001, p= 0.012, respectively) according to TTS. It is considered that CRP, a powerful marker of inflammation, is related with severity of pneumonia and a high level of CRP may be useful to make a decision about hospitalisation.