Time to sputum conversion in patients with pulmonary tuberculosis: A score to estimate the infectious period.

Introduction: Patients with pulmonary tuberculosis (PTB) disease and positive sputum cultures are the main source of infection. Culture conversion time is inconsistent and defining the length of respiratory isolation is challenging. The objective of this study is to develop a score to predict the length of isolation period. Methods: A retrospective study was carried out to evaluated risk factors associated with persistent positive sputum cultures after 4 weeks of treatment in 229 patients with PTB. A multivariable logistic regression model was used to determinate predictors for positive culture and a scoring system was created based on the coefficients of the final model. Results: Sputum culture was persistently positive in 40.6%. Fever at consultation (1.87, 95% CI:1.02-3.41), smoking (2.44, 95% CI:1.36-4.37), >2 affected lung lobes (1.95, 95% CI:1.08-3.54), and neutrophil-to-lymphocyte ratio > 3.5 (2.22, 95% CI:1.24-3.99), were significantly associated with delayed culture conversion. Therefore, we assembled a severity score that achieved an area under the curve of 0.71 (95% CI:0.64-0.78). Conclusions: In patients with smear positive PTB, a score with clinical, radiological and analytical parameters can be used as a supplemental tool to assist clinical decisions in isolation period.

Gastroenteritis aguda y Haemophilus parainfluenzae: una asociación previsible pero no reportada / Acute gastroenteritis and Haemophilus parainfluenzae: An unreported but predictable association

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The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms.

Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p < 0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82-0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms.

A pilot study on the diagnostic accuracy of proadrenomedullin and proatrial natriuretic Peptide in lower respiratory tract infections.

BACKGROUND: Pneumonia is the leading cause of death among infectious diseases in developed countries. However, the severity of pneumonia requiring hospitalization often makes the initial diagnosis difficult because of an equivocal clinical picture or interpretation of the chest film. The objective of the present study was to assess the usefulness of the plasma levels of mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) in differentiating pneumonia from other lower respiratory tract infections (LRTIs). METHODS: A retrospective study was conducted. The plasma levels of MR-proADM and MR-proANP were measured in 85 patients hospitalized for LRTIs, 56 of whom with diagnosis of pneumonia and 29 with other LRTIs. RESULTS: The patients with pneumonia had increased MR-proADM levels (median 1.46 nmol/L [IQR 25-75, 0.82-2.02 nmol/L]) compared with the patients with other LRTIs (median 0.88 nmol/mL [0.71-1.39 nmol/L]) (p= 0.04). However, the MR-proANP levels did not show differences between the groups. The optimal threshold of MR-proADM to predict pneumonia was 1.5 nmol/L, which yielded a sensitivity of 51.7% (95% CI, 38.0-65.3), a 79.3% specificity (95% CI, 60.3-92.0), and an odds ratio of 6.64 (95% CI, 1.32-32.85). The combination of this parameter with C-reactive protein in an "and" rule increased the specificity for detecting pneumonia significantly. CONCLUSION: MR-proADM levels (but not MR-proANP levels) are increased in patients with pneumonia although its discriminatory power is moderate.

Estudio de contactos según círculos concéntricos en un caso de tuberculosis laríngea / Contact investigation according to concentric circles in a case of laryngeal tuberculosis

Objetivo: Describir el censo y el estudio de contactos en un caso de tuberculosis laríngea. Métodos: A partir de un paciente con tuberculosis laríngea y mediante entrevistas e inspección se establecieron tres círculos de contactos. Se realizó la prueba de la tuberculina (positiva ≥ 5mm) y a los positivos se les propuso realizarse una radiografía de tórax. La asociación con la infección se midió con la odds ratio. La relación dosis-respuesta se determinó con el test de χ2 de tendencia lineal. Resultados: La prevalencia de infección fue del 39,9% (67/168). Entre los compañeros de trabajo con mayor convivencia fue del 60,0% (24/40), entre los del bar del 43,3% (13/30) y la tasa de virajes fue del 12,9%. Se observó relación con el grado de exposición (p<0,0001). Conclusiones: La tuberculosis laríngea tuvo una alta transmisión en la empresa y en el bar. Deben realizarse estudios exhaustivos y buena comunicación a los expuestos (AU)

Objective: To describe the census and contact investigation in a case of laryngeal tuberculosis. Methods: Based on a patient with laryngeal tuberculosis and through interviews and ocular inspection, we established three circles of contacts. The tuberculin test was performed (positive ≥ 5mm). Persons testing positive were invited to undergo a chest x-ray. The association of the infection was calculated with the odds ratio. The exposure-response relationship was determined with the linear trend χ2 test. Results: The overall prevalence of infection was 39.9% (67/168). The prevalence among coworkers was 60.0% (24/40), that among frequenters of the town bar was 43.3% (13/30) and the conversions rate was 12.9%. There was a relationship with the degree of exposure (p <0.0001). Conclusions: Laryngeal tuberculosis involved high transmission to coworkers and frequenters of the town bar. In-depth studies through concentric circles and good communication with exposed individuals should be carried out (AU)

Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.

BACKGROUND: Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay. METHODS AND FINDINGS: We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults. CONCLUSIONS: Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

Guía multidisciplinar para la valoración pronóstica, diagnóstico y tratamiento de la neumonía adquirida en la comunidad / Multidisciplinary guidelines for the management of community-acquired pneumonia

La neumonía adquirida en la comunidad (NAC) es una enfermedad infecciosa respiratoria aguda que tiene una incidencia que oscila entre 3 y 8 casos por 1.000 habitantes por año. Esta incidencia aumenta con la edad y las comorbilidades. El 40% de los pacientes con NAC requieren ingreso hospitalario y alrededor del 10% necesitan ser admitidos en una Unidad de Cuidados Intensivos (UCI). La mortalidad global de la NAC está alrededor del 10%. Diversos estudios han sugerido que la implementación de guías clínicas mejora la evolución del paciente tanto en mortalidad como en estancia hospitalaria. Las guías clínicas más recientes y más utilizadas son la de la Infectious Diseases Society of America/American Thoracic Society, publicada en 2007, la de la British Thoracic Society, publicada en 2009, y la de la European Respiratory Society en colaboracio´n con la European Society of Clinical Microbiology and Infectious Diseases, publicada en 2011. En España, la más reciente es la normativa de la Sociedad Española de Neumología y Cirugía Torácica, publicada en el año 2010. La presente guía clínica GNAC es multidisciplinar y ha contado con la ayuda del Centro Cochrane Iberoamericano (CCIB) para la síntesis de las guías previas y la selección de la bibliografía. Esta guía clínica está diseñada para ser utilizada por todos los profesionales que pueden participar en el proceso asistencial de la NAC en sus vertientes diagnóstica, de caracterización de la gravedad, de tratamiento y de prevención. Para cada uno de los siguientes apartados se han desarrollado tablas con recomendaciones donde se clasifica su evidencia, la fortaleza de la misma y su aplicabilidad práctica según la clasificación Grading of Recommendations of Assessment Development and Evaluations (GRADE): 1. Epidemiología, etiología microbiana y resistencias microbianas. 2. Diagnóstico clínico y microbiológico. 3. Escalas pronósticas y decisión de ingreso hospitalario. 4. Criterios de ingreso en la UCI. 5. Tratamiento antibiótico empírico y tratamiento antibiótico definitivo. 6. Falta de respuesta al tratamiento antibiótico. 7. Vacunaciones en la prevención de la NAC (AU)

Community-acquired pneumonia (CAP) is an infectious respiratory disease with an incidence that ranges from 3 to 8 cases per 1,000 inhabitants per year. This incidence increases with age and comorbidities. Forty per cent of CAP patients require hospitalization and around 10% of these patients are admitted in an Intensive Care Unit (ICU). Several studies have suggested that the implementation of clinical guidelines has a positive impact in the outcome of patients including mortality and length of stay. The more recent and used guidelines are those from Infectious Diseases Society of America/American Thoracic Society, published in 2007, the 2009 from the British Thoracic Society, and that from the European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases, published in 2010. In Spain, the most recently released guideline is the Sociedad Española de Neumología y Cirugía Torácica-2011 guideline. The present guidelines GNAC are designed to be used by the majority of health-care professionals that can participate in the care of CAP patients including diagnosis, decision of hospital and ICU admission, treatment and prevention. The Centro Cochrane Iberoamericano (CCIB) has participated in summarizing the previous guidelines and in the bibliography search. For each one of the following sections the panel of experts has developed a table with recommendations classified according to its evidence, strength and practical applicability using the Grading of Recommendations of Assessment Development and Evaluations (GRADE) system: 1. Epidemiology, microbiological etiology and antibiotic resistances. 2. Clinical and microbiological diagnosis. 3. Prognostic scales and decision of hospital admission. 4. ICU admission criteria. 5. Empirical and definitive antibiotic treatment. 6. Treatment failure. 7. Prevention (AU)

[Multidisciplinary guidelines for the management of community-acquired pneumonia]. / Guía multidisciplinar para la valoración pronóstica, diagnóstico y tratamiento de la neumonía adquirida en la comunidad.

Community-acquired pneumonia (CAP) is an infectious respiratory disease with an incidence that ranges from 3 to 8 cases per 1,000 inhabitants per year. This incidence increases with age and comorbidities. Forty per cent of CAP patients require hospitalization and around 10% of these patients are admitted in an Intensive Care Unit (ICU). Several studies have suggested that the implementation of clinical guidelines has a positive impact in the outcome of patients including mortality and length of stay. The more recent and used guidelines are those from Infectious Diseases Society of America/American Thoracic Society, published in 2007, the 2009 from the British Thoracic Society, and that from the European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases, published in 2010. In Spain, the most recently released guideline is the Sociedad Española de Neumología y Cirugía Torácica-2011 guideline. The present guidelines GNAC are designed to be used by the majority of health-care professionals that can participate in the care of CAP patients including diagnosis, decision of hospital and ICU admission, treatment and prevention. The Centro Cochrane Iberoamericano (CCIB) has participated in summarizing the previous guidelines and in the bibliography search. For each one of the following sections the panel of experts has developed a table with recommendations classified according to its evidence, strength and practical applicability using the Grading of Recommendations of Assessment Development and Evaluations (GRADE) system: 1. Epidemiology, microbiological etiology and antibiotic resistances.2. Clinical and microbiological diagnosis.3. Prognostic scales and decision of hospital admission.4. ICU admission criteria. 5. Empirical and definitive antibiotic treatment.6. Treatment failure. 7. Prevention.

[Contact investigation according to concentric circles in a case of laryngeal tuberculosis]. / Estudio de contactos según círculos concéntricos en un caso de tuberculosis laríngea.

OBJECTIVE: To describe the census and contact investigation in a case of laryngeal tuberculosis. METHODS: Based on a patient with laryngeal tuberculosis and through interviews and ocular inspection, we established three circles of contacts. The tuberculin test was performed (positive ≥5 mm). Persons testing positive were invited to undergo a chest x-ray. The association of the infection was calculated with the odds ratio. The exposure-response relationship was determined with the linear trend χ2 test. RESULTS: The overall prevalence of infection was 39.9% (67/168). The prevalence among coworkers was 60.0% (24/40), that among frequenters of the town bar was 43.3% (13/30) and the conversions rate was 12.9%. There was a relationship with the degree of exposure (p <0.0001). CONCLUSIONS: Laryngeal tuberculosis involved high transmission to coworkers and frequenters of the town bar. In-depth studies through concentric circles and good communication with exposed individuals should be carried out.

Pleural fluid C-reactive protein contributes to the diagnosis and assessment of severity of parapneumonic effusions.

BACKGROUND AND AIMS: Prompt identification of parapneumonic effusions has immediate therapeutic benefits. We aimed to assess whether C-reactive protein (CRP) and routine biochemistries in pleural fluid are accurate markers of parapneumonic effusions, and to evaluate their properties as indicators for drainage (complicated parapneumonic effusion). METHODS: A retrospective review of 340 non-purulent parapneumonic effusions and 1,659 non-parapneumonic exudates from a single center was performed and the discriminative properties of pleural fluid routine biochemistries and, when available, CRP were evaluated. CRP, along with classical fluid parameters, was also applied to classify patients as having complicated or uncomplicated parapneumonic effusions. ROC analysis established the threshold of CRP for discriminating between groups. RESULTS: Pleural fluids with neutrophilic predominance and CRP levels >45 mg/dL were most likely to be parapneumonic in origin (likelihood ratio=7.7). When attempting to differentiate non-purulent complicated from uncomplicated effusions, a CRP >100mg/L had the same performance characteristics (area under the curve=0.81) as the widely accepted biochemistries pH and glucose. Combinations of CRP with pH or glucose resulted in incrementally discriminating values, pertaining to either sensitivity (75-80%) or specificity (97%), for complicated effusions. CONCLUSION: Pleural fluid CRP may be a useful adjunctive test in pleural effusions, both as a marker of parapneumonics and, particularly, as a differentiator between complicated and uncomplicated effusions.

Triggering receptor (TREM-1) expressed on myeloid cells predicts bacteremia better than clinical variables in community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Some clinical variables are associated with bacteremia in patients with community-acquired pneumonia (CAP). The aim of this study was to analyse the accuracy of the soluble form of triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict positive blood cultures in comparison with established clinical prognostic variables. METHODS: In addition to collecting clinical and laboratory information, a commercially available immunoassay kit was used to measure the serum sTREM-1 levels on the first day of admit ion in patients with CAP. Receiver operating characteristic (ROC) curves were used to compare the ability of sTREM-1 and commonly used clinical variables to identify bacteremia. RESULTS: Blood cultures yielded a pathogen in 13 (10.4%) out of 124 patient samples. The microorganisms isolated were Streptococcus pneumoniae (11 patients) and Klebsiella pneumoniae (2 patients). The presence of pleuritic chest pain, tachycardia and extreme white cell count (WCC) were associated with bacteremia. However, ROC curve analysis showed an accuracy of sTREM-1 (area under the receiver operating characteristic curve (AUC) 0.84, 95% CI: 0.72-0.95), which was higher than pleuritic chest pain (AUC 0.71, 95% CI: 0.57-0.84), tachycardia (AUC 0.73, 95% CI: 0.58-0.88) and extreme WCC (AUC 0.70, 95% CI: 0.55-0.85) for predicting positive blood cultures. Low admission sTREM-1 serum values had a high negative predictive value for excluding bacteremia (sTREM-1 <120 pg/mL = 98.8%). CONCLUSIONS: This preliminary study suggests that the determination of sTREM-1 serum levels on admission may be more accurate than clinical variables for identifying bacteremic patients.

C-reactive protein for discriminating treatment failure from slow responding pneumonia.

BACKGROUND: The management of patients with community-acquired pneumonia (CAP) who fail to improve constitutes a challenge for clinicians. This study investigated the usefulness of C-reactive protein (CRP) changes in discriminating true treatment failure from slow response to treatment. METHODS: This prospective multicenter observational study investigated the behavior of plasma CRP levels on days 1 and 4 in hospitalized patients with CAP. We identified non-responding patients as those who had not reached clinical stability by day 4. Among them, true treatment failure and slow response situations were defined when initial therapy had to be changed or not after day 4 by attending clinicians, respectively. RESULTS: By day 4, 78 (27.4%) out of 285 patients had not reached clinical stability. Among them, 56 (71.8%) patients were cured without changes in initial therapy (mortality 0.0%), and in 22 (28.2%) patients, the initial empirical therapy needed to be changed (mortality 40.9%). By day 4, CRP levels fell in 52 (92.9%) slow responding and only in 7 (31.8%) late treatment failure patients (p<0.001). A model developed including CRP behavior and respiratory rate at day 4 identified treatment failure patients with an area under the Receiver Operating Characteristic curve of 0.87 (CI 95%, 0.78-0.96). CONCLUSION: Changes in CRP levels are useful to discriminate between true treatment failure and slow response to treatment and can help clinicians in management decisions when CAP patients fail to improve.

A prediction rule for estimating the risk of bacteremia in patients with community-acquired pneumonia.

BACKGROUND: We endeavored to construct a simple score based entirely on epidemiological and clinical variables that would stratify patients who require hospital admission because of community-acquired pneumonia into groups with a low or high risk of developing bacteremia. METHODS: Derivation and internal validation cohorts were obtained by retrospective analysis of a database that included 3116 consecutive patients with community-acquired pneumonia from 2 university hospitals. Potential predictive factors were determined by means of a multivariate logistic regression equation applied to a cohort consisting of 60% of the patients. Points were assigned to significant parameters to generate the score. It was then internally validated with the remaining 40% of patients and was externally validated using an independent multicenter cohort of 1369 patients. RESULTS: The overall rates of bacteremia were 12%-16% in the cohorts. The clinical probability estimate of developing bacteremia was based on 6 variables: liver disease, pleuritic pain, tachycardia, tachypnea, systolic hypotension, and absence of prior antibiotic treatment. For the score, 1 point was assigned to each predictive factor. In the derivation cohort, a cutoff score of 2 best identified the risk of bacteremia. In the validation cohorts, rates of bacteremia were <8% for patients with a score 1 (43%-49% of patients), whereas blood culture results were positive in 14%-63% of cases for patients with a score 2. CONCLUSIONS: This clinical score, based on readily available and objective variables, provides a useful tool to predict bacteremia. The score has been internally and externally validated and may be useful to guide diagnostic decisions for community-acquired pneumonia.

Risk factors and outcome of community-acquired pneumonia due to Gram-negative bacilli.

BACKGROUND AND OBJECTIVE: Several sets of guidelines have advocated initial antibiotic treatment for community-acquired pneumonia due to Gram-negative bacilli in patients with specific risk factors. However, evidence to support this recommendation is scarce. We sought to identify risk factors for community-acquired pneumonia due to Gram-negative bacilli, including Pseudomonas aeruginosa, and to assess outcomes. METHODS: An observational analysis was carried out on prospectively collected data for immunocompetent adults hospitalized for community-acquired pneumonia in two acute-care hospitals. Cases of pneumonia due to Gram-negative bacilli were compared with those of non-Gram-negative bacilli causes. RESULTS: Sixty-one (2%) of 3272 episodes of community-acquired pneumonia were due to Gram-negative bacilli. COPD (odds ratio (OR) 2.4, 95% confidence interval (CI): 1.2-5.1), current use of corticosteroids (OR 2.8, 95% CI: 1.2-6.3), prior antibiotic therapy (OR 2.6, 95% CI: 1.4-4.8), tachypnoea >or=30 cycles/min (OR 2.1, 95% CI: 1.1-4.2) and septic shock at presentation (OR 6.1, 95% CI: 2.5-14.6) were independently associated with Gram-negative bacilli pneumonia. Initial antibiotic therapy in patients with pneumonia due to Gram-negative bacilli was often inappropriate. These patients were also more likely to require admission to the intensive care unit, had longer hospital stays, and higher early (<48 h) (21% vs 2%; P < 0.001) and overall mortality (36% vs 7%; P < 0.001). CONCLUSIONS: These results suggest that community-acquired pneumonia due to Gram-negative bacilli is uncommon, but is associated with a poor outcome. The risk factors identified in this study should be considered when selecting initial antibiotic therapy for patients with community-acquired pneumonia.

C-reactive protein and other predictors of poor outcome in patients hospitalized with exacerbations of chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: CRP is elevated in patients with acute exacerbations of COPD (AECOPD), but there is little information on whether this biomarker can help to identify adverse short-term clinical outcomes. METHODS: A 6-month prospective study of all patients with AECOPD requiring hospital admission. Clinical, laboratory (including plasma CRP levels at admission) and functional data were recorded. The outcome variable (the adverse outcome) consisted of: (i) death in hospital or within 15 days of discharge, (ii) transfer to the intensive care unit, or (iii) development of acute heart failure during hospitalization. RESULTS: Data from 147 patients with a total of 160 admissions were recorded. During follow up, 38 (23.7%) adverse outcomes were observed, including 13 (8.8%) and 8 (5.4%) patients who died during hospitalization or within 15 days of discharge, respectively. CRP at a level of 50 mg/L was related to an adverse outcome (OR 4.9, 95% CI: 1.92-12.6, P < 0.01), although by itself it was neither sensitive nor specific (area under the receiver operating characteristic curve (AUC) 0.69, 95% CI: 0.60-0.77). However, a risk score derived from the combination of CRP with other variables, such as 'current smoker', 'at least two comorbidities' and 'confusion,' at admission showed good predictive ability to identify an adverse outcome (AUC of 0.80, 95% CI: 0.72-0.88). CONCLUSIONS: Plasma CRP in combination with other variables obtained at admission may assist identification of high-risk patients with AECOPD.

Pharmacotherapy of pneumonia occurring in older patients.

The elderly population is characterized by several baseline conditions that increase the risk and modify the etiology of pneumonia. Immunosuppression caused by either concomitant morbidities or treatments, susceptibility to aspiration, residency in long-term facilities, or frequent use of antimicrobials are some factors that need serious consideration in selecting the most appropriate treatment. In the absence of these conditions, pneumonia can be treated according to locally adapted international guidelines; however, specific diagnostic and therapeutic strategies should be applied in the presence of these parameters, providing coverage for more resistant agents. Polymedication by the elderly poses a high risk for potentially severe drug interactions; consequently, modifications of dosages may be necessary along with close monitoring for clinical signs of adverse effects or serum levels of some drugs. Wide influenza and pneumococcal vaccines can significantly contribute to improving the future of the disease.