细菌性肺炎球菌肺炎:来自单一中心的279名成人患者的纵向研究

J. Gentile, C. Hernandez, M. Sparo, E. Rodríguez, C. Ceriani, Florencia Bruggesser
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Non-respiratory symptoms occurred in 50% of cases. Infiltrates on chest x ray were predominantly unilateral (75%) and lobar (57%). Regarding severity, a low PSI score I-II-II was found in 178 patients (64%), 60 (22%) were admitted to ICU, 40 (14%) required mechanical ventilation, and 21 (8%) developed empyema. Penicillin resistance was not found. Mortality was 18% (49/279), and by a multivariate analysis it was associated with confusion (OR= 5.44), age>80 years (OR =5.72), leukopenia (OR =5.73) and dyspnea (OR=7.87). Conclusions: In this study of 279 bacteremic pneumococcal pneumonia we reinforce previous knowledge on this disease regarding incidence and clinical features and confirm a considerable an early mortality associated to age and severity of disease at onset. Recent changes in incidence of BPP in adults could be secondary to herd effect of PVC 13 a vaccine that is mandatory in children in our community since 2012. DOI: 10.18297/jri/vol2/iss1/10 Received Date: February 13, 2018 Accepted Date: March 29, 2018 Website: https://ir.library.louisville.edu/jri Affiliations: 1 Servicio de Infectología, Hospital Santamarina, Tandil, Argentina 2 Laboratorio de Microbiología, Hospital Santamarina, Tandil, Argentina 3 Area de Bioestadística, FCV-UNCPBA 4 Area de virología, FCV-UNCPBA, CIVETAN-CONICET ©2018, The Author(s). 47 ULJRI Vol 2, (1) 2018 ORIGINAL RESEARCH *Correspondence To: Dr. Jorge Gentile Work Address: Uriburu 950 Tandil CP 7000-Argentina, Work Email: gentilejorgeh@gmail.com treated in ambulatory setting between 1989 and 2015. Exclusion criteria: having been hospitalized in the last 30 days, or presented with any other evidence suggestive of nosocomial pneumonia, severe immunosuppression such in transplantation, AIDS or receiving chemotherapy or other immunosuppressive drugs. Study definitions/variables Pneumonia was defined as the presence of a new infiltrate on chest radiograph plus two or more of the following clinical manifestations including: fever (axillary temperature >37.8oC), cough, production of purulent sputum, pleuritic chest pain and dyspnoea. BPP was defined as a diagnosis of pneumonia with one or more positive blood cultures for S. pneumoniae. Identification of patients with BPP: one of the authors of this manuscript, (CH or JG), or a resident, reviewed admissions to the hospital daily, including holidays. The laboratory informed as soon as possible, when S. pneumoniae was isolated from blood culture. Data of chart was reviewed and a form was completed within 48-72h of admission. All patients were questioned, examined and followed exclusively by the authors. (JG or CH). When a patient with criteria of BPP was not admitted and sent home we strived to contact him in order to assist and include him in the study. Hospital based incidence was calculated dividing number of BPP/adult patients admitted annually to the hospital x 1000. Seasonal distribution was registered. Population incidence, was calculated during the period 20102015, adding to our series of patients with BPP admitted to the other two centres of the city, and considering population variations in the period. The following variables were recorded on admission directly from the subject, or from documentation in chart or interview with relatives: age, sex, duration of illness before consult, underlying chronic conditions such as diabetes, chronic renal failure, congestive heart failure, chronic lung disease, neurologic disease, malignancies, HIV infection, alcoholism, hepatic disease, smoking, prior antimicrobial therapy as well as clinical signs and symptoms. Living in nursing home or homelessness was registered too. Patients with dull percussion and bronchial breathing sounds on auscultation were considered as having clinical consolidation. Hypotension was defined as systolic arterial tension below 90mmHg. Abdominal pain, vomiting, hypotension, and confusion were considered nonpulmonary symptoms. Classical pneumococcal infection was considered if patients had all four of the following features: fever, pleuritic chest pain, lobar consolidation on chest X ray and leucocytosis. Pleural fluid examination was performed in all patients with pleural effusion. Empyema was considered when macroscopic pus or bacteria were identified in pleural fluid. History of pneumococcal vaccination was recorded in all cases and considered positive in patients who had received at least a single dose of 23-valent pneumococcal polysaccharide vaccine within the last 5 years. On admission, patients were stratified into risk classes I to V based on Pneumonia Severity Index (PSI) score [6]. Laboratory Leukocytosis was considered when white blood cells were more than 12,000/ml and leukopenia when WBC <4,000/ml Microbiological Testing S. pneumoniae was identified using standard microbiology procedures. One set of blood cultures were collected from each patient at entry, which is considered standard of care for patients with CAP admitted to the hospital. Conventional broth culture using nutritionally enriched media was used until 1997, after which fully automated, continuous blood culture monitoring equipment (BacT/ALERT® 3D BioMérieux, Inc. 100 Rodolphe Street, Durham, NC) became available. High quality sputum specimens (containing <10 squamous epithelial cells and >25 Polymorph Nuclear cells per low power field) were processed for bacterial diagnosis. Briefly, sputum was homogenized in 1.2 ml of sterile saline, spread onto a glass slide, air dried and heat fixed. Strains were identified based on Gram stains and morphology: gram-positive cocci found in singles, in pairs or in short chains were indicative of pneumococci infection. Sputum samples were inoculated on blood agar and chocolate agar plates and incubated at 35oC with 5-10% CO2 for 72 hours. All S. pneumoniae isolates were tested for penicillin susceptibility by diffusion, using 1 μg oxacillin disks and by broth micro-dilution test. Isolates were also screened for susceptibility to erythromycin, tetracycline, and levofloxacin using disk diffusion method. In addition, minimum inhibitory concentration (MIC) tests were used to determine susceptibility to erythromycin, extended spectrum cephalosporins, fluoroquinolones, tetracycline, trimethoprim sulfametoxazol, clindamycin, cefuroxime and vancomycin, in accordance to Clinical and Laboratory Standards Institute (CLSI, 2012) established guidelines [7]. 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Multiple logistic regression analyses was performed to evaluate those factors found to be significant by univariate analysis and previously hypothesized to affect mortality. Two-tailed p-values are reported, with statistical significance when p<0.05. SAS V9.3 statistical software was used for calculations (SAS, Institute Inc. Cary, NC, USA). 48 ULJRI Vol 2, (1) 2018","PeriodicalId":91979,"journal":{"name":"The University of Louisville journal of respiratory infections","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bacteremic Pneumococcal Pneumonia: a Longitudinal Study in 279 Adult Patients from\\n a Single Center\",\"authors\":\"J. Gentile, C. Hernandez, M. Sparo, E. Rodríguez, C. 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Regarding severity, a low PSI score I-II-II was found in 178 patients (64%), 60 (22%) were admitted to ICU, 40 (14%) required mechanical ventilation, and 21 (8%) developed empyema. Penicillin resistance was not found. Mortality was 18% (49/279), and by a multivariate analysis it was associated with confusion (OR= 5.44), age>80 years (OR =5.72), leukopenia (OR =5.73) and dyspnea (OR=7.87). Conclusions: In this study of 279 bacteremic pneumococcal pneumonia we reinforce previous knowledge on this disease regarding incidence and clinical features and confirm a considerable an early mortality associated to age and severity of disease at onset. Recent changes in incidence of BPP in adults could be secondary to herd effect of PVC 13 a vaccine that is mandatory in children in our community since 2012. DOI: 10.18297/jri/vol2/iss1/10 Received Date: February 13, 2018 Accepted Date: March 29, 2018 Website: https://ir.library.louisville.edu/jri Affiliations: 1 Servicio de Infectología, Hospital Santamarina, Tandil, Argentina 2 Laboratorio de Microbiología, Hospital Santamarina, Tandil, Argentina 3 Area de Bioestadística, FCV-UNCPBA 4 Area de virología, FCV-UNCPBA, CIVETAN-CONICET ©2018, The Author(s). 47 ULJRI Vol 2, (1) 2018 ORIGINAL RESEARCH *Correspondence To: Dr. Jorge Gentile Work Address: Uriburu 950 Tandil CP 7000-Argentina, Work Email: gentilejorgeh@gmail.com treated in ambulatory setting between 1989 and 2015. Exclusion criteria: having been hospitalized in the last 30 days, or presented with any other evidence suggestive of nosocomial pneumonia, severe immunosuppression such in transplantation, AIDS or receiving chemotherapy or other immunosuppressive drugs. Study definitions/variables Pneumonia was defined as the presence of a new infiltrate on chest radiograph plus two or more of the following clinical manifestations including: fever (axillary temperature >37.8oC), cough, production of purulent sputum, pleuritic chest pain and dyspnoea. BPP was defined as a diagnosis of pneumonia with one or more positive blood cultures for S. pneumoniae. Identification of patients with BPP: one of the authors of this manuscript, (CH or JG), or a resident, reviewed admissions to the hospital daily, including holidays. The laboratory informed as soon as possible, when S. pneumoniae was isolated from blood culture. Data of chart was reviewed and a form was completed within 48-72h of admission. All patients were questioned, examined and followed exclusively by the authors. (JG or CH). When a patient with criteria of BPP was not admitted and sent home we strived to contact him in order to assist and include him in the study. Hospital based incidence was calculated dividing number of BPP/adult patients admitted annually to the hospital x 1000. Seasonal distribution was registered. Population incidence, was calculated during the period 20102015, adding to our series of patients with BPP admitted to the other two centres of the city, and considering population variations in the period. The following variables were recorded on admission directly from the subject, or from documentation in chart or interview with relatives: age, sex, duration of illness before consult, underlying chronic conditions such as diabetes, chronic renal failure, congestive heart failure, chronic lung disease, neurologic disease, malignancies, HIV infection, alcoholism, hepatic disease, smoking, prior antimicrobial therapy as well as clinical signs and symptoms. Living in nursing home or homelessness was registered too. Patients with dull percussion and bronchial breathing sounds on auscultation were considered as having clinical consolidation. Hypotension was defined as systolic arterial tension below 90mmHg. Abdominal pain, vomiting, hypotension, and confusion were considered nonpulmonary symptoms. Classical pneumococcal infection was considered if patients had all four of the following features: fever, pleuritic chest pain, lobar consolidation on chest X ray and leucocytosis. Pleural fluid examination was performed in all patients with pleural effusion. Empyema was considered when macroscopic pus or bacteria were identified in pleural fluid. History of pneumococcal vaccination was recorded in all cases and considered positive in patients who had received at least a single dose of 23-valent pneumococcal polysaccharide vaccine within the last 5 years. On admission, patients were stratified into risk classes I to V based on Pneumonia Severity Index (PSI) score [6]. Laboratory Leukocytosis was considered when white blood cells were more than 12,000/ml and leukopenia when WBC <4,000/ml Microbiological Testing S. pneumoniae was identified using standard microbiology procedures. One set of blood cultures were collected from each patient at entry, which is considered standard of care for patients with CAP admitted to the hospital. Conventional broth culture using nutritionally enriched media was used until 1997, after which fully automated, continuous blood culture monitoring equipment (BacT/ALERT® 3D BioMérieux, Inc. 100 Rodolphe Street, Durham, NC) became available. High quality sputum specimens (containing <10 squamous epithelial cells and >25 Polymorph Nuclear cells per low power field) were processed for bacterial diagnosis. Briefly, sputum was homogenized in 1.2 ml of sterile saline, spread onto a glass slide, air dried and heat fixed. 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引用次数: 0

摘要

背景:细菌性肺炎球菌性肺炎(BPP)是侵袭性肺炎球菌病(IPD)最常见的临床表现。尽管对这一问题进行了广泛的研究,但我们区域对疾病负担、人口和结果特征的了解甚少。方法:为了加深我们对阿根廷坦迪尔社区医院BPP成年患者特征的了解,我们对1989 - 2015年BPP患者进行了前瞻性、纵向、观察性研究。结果:共纳入279例患者。平均发病率为2.8/1000,近两年急剧下降,为0.8/1000。患者平均年龄60岁。65%的病例存在合并症。50%的病例出现非呼吸道症状。胸部x线上的浸润主要是单侧(75%)和大叶(57%)。在严重程度方面,178例(64%)患者PSI评分为I-II-II, 60例(22%)入住ICU, 40例(14%)需要机械通气,21例(8%)发生脓胸。未发现青霉素耐药。死亡率为18%(49/279),通过多因素分析,与混淆(OR= 5.44)、年龄>80岁(OR= 5.72)、白细胞减少(OR= 5.73)和呼吸困难(OR=7.87)相关。结论:在这项对279例细菌性肺炎球菌肺炎的研究中,我们加强了以前对这种疾病的发病率和临床特征的认识,并确认了发病时年龄和疾病严重程度相关的相当大的早期死亡率。最近成人BPP发病率的变化可能继发于PVC 13疫苗的群体效应,PVC 13疫苗自2012年起在我们社区的儿童中强制接种。DOI: 10.18297/jri/vol2/iss1/10收件日期:2018年2月13日收件日期:2018年3月29日网站:https://ir.library.louisville.edu/jri所属机构:1 Servicio de Infectología, Hospital Santamarina, Tandil, Argentina 2 Laboratorio de Microbiología, Hospital Santamarina, Tandil, Argentina 3 Area de Bioestadística, FCV-UNCPBA 4 Area de virología, FCV-UNCPBA, CIVETAN-CONICET©2018,作者。通讯作者:Dr. Jorge Gentile工作地址:Uriburu 950 Tandil CP 7000-阿根廷,工作邮箱:gentilejorgeh@gmail.com 1989 - 2015年在门诊治疗。排除标准:在过去30天内住院,或有任何其他证据表明有院内肺炎、严重免疫抑制(如移植、艾滋病)或接受化疗或其他免疫抑制药物。研究定义/变量肺炎被定义为胸片上出现新的浸润并伴有以下两种或两种以上的临床表现,包括:发热(腋窝温度>37.8℃)、咳嗽、产生化脓性痰、胸膜炎性胸痛和呼吸困难。BPP被定义为一种或多种肺炎链球菌血培养阳性的肺炎诊断。BPP患者的识别:本文的作者之一(CH或JG)或住院医师每天都会检查医院的入院情况,包括假期。当从血培养中分离出肺炎链球菌时,实验室尽快通知。在入院后48-72h内查阅病历资料并填写表格。所有患者均由作者单独询问、检查和跟踪。(JG或CH)。当一名有BPP标准的患者没有入院并被送回家时,我们努力联系他以协助并将他纳入研究。以医院为基础的发病率计算BPP/每年入院的成人患者数× 1000。登记季节分布。人口发病率是在2010 - 2015年期间计算的,加入了我们在城市其他两个中心入院的BPP患者系列,并考虑了这一时期的人口变化。以下变量在入院时直接从受试者处记录,或从图表文件或亲属访谈中记录:年龄、性别、会诊前疾病持续时间、潜在慢性疾病,如糖尿病、慢性肾衰竭、充血性心力衰竭、慢性肺病、神经系统疾病、恶性肿瘤、HIV感染、酗酒、肝病、吸烟、既往抗微生物治疗以及临床体征和症状。住在养老院或无家可归者也被登记在案。听诊有沉闷的叩击声和支气管呼吸音者视为临床巩固。低血压定义为收缩期动脉张力低于90mmHg。腹痛、呕吐、低血压和精神错乱被认为是非肺部症状。如果患者具有以下四种特征:发热、胸膜炎性胸痛、胸片上的大叶实变和白细胞增多,则考虑为典型肺炎球菌感染。所有胸腔积液患者均行胸腔积液检查。
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Bacteremic Pneumococcal Pneumonia: a Longitudinal Study in 279 Adult Patients from a Single Center
Background: Bacteremic pneumococcal pneumonia (BPP) is the most common clinical presentation of invasive pneumococcal disease (IPD). Although it has been extensively studied, there is little knowledge in our region in relation to burden of disease, demographic and outcome features. Methods: We conducted a prospective, longitudinal, observational study from 1989 to 2015 in adult patients with BPP, in order to deepen our knowledge of the characteristics of this disease in our community hospital in Tandil, Argentina. Results: 279 patients were included. The mean incidence was 2.8/1000 admissions with a sharp decrease in the last two years, reaching 0.8/1000 admissions. Mean patient age was 60 years. Comorbidities were found in 65% of the cases. Non-respiratory symptoms occurred in 50% of cases. Infiltrates on chest x ray were predominantly unilateral (75%) and lobar (57%). Regarding severity, a low PSI score I-II-II was found in 178 patients (64%), 60 (22%) were admitted to ICU, 40 (14%) required mechanical ventilation, and 21 (8%) developed empyema. Penicillin resistance was not found. Mortality was 18% (49/279), and by a multivariate analysis it was associated with confusion (OR= 5.44), age>80 years (OR =5.72), leukopenia (OR =5.73) and dyspnea (OR=7.87). Conclusions: In this study of 279 bacteremic pneumococcal pneumonia we reinforce previous knowledge on this disease regarding incidence and clinical features and confirm a considerable an early mortality associated to age and severity of disease at onset. Recent changes in incidence of BPP in adults could be secondary to herd effect of PVC 13 a vaccine that is mandatory in children in our community since 2012. DOI: 10.18297/jri/vol2/iss1/10 Received Date: February 13, 2018 Accepted Date: March 29, 2018 Website: https://ir.library.louisville.edu/jri Affiliations: 1 Servicio de Infectología, Hospital Santamarina, Tandil, Argentina 2 Laboratorio de Microbiología, Hospital Santamarina, Tandil, Argentina 3 Area de Bioestadística, FCV-UNCPBA 4 Area de virología, FCV-UNCPBA, CIVETAN-CONICET ©2018, The Author(s). 47 ULJRI Vol 2, (1) 2018 ORIGINAL RESEARCH *Correspondence To: Dr. Jorge Gentile Work Address: Uriburu 950 Tandil CP 7000-Argentina, Work Email: gentilejorgeh@gmail.com treated in ambulatory setting between 1989 and 2015. Exclusion criteria: having been hospitalized in the last 30 days, or presented with any other evidence suggestive of nosocomial pneumonia, severe immunosuppression such in transplantation, AIDS or receiving chemotherapy or other immunosuppressive drugs. Study definitions/variables Pneumonia was defined as the presence of a new infiltrate on chest radiograph plus two or more of the following clinical manifestations including: fever (axillary temperature >37.8oC), cough, production of purulent sputum, pleuritic chest pain and dyspnoea. BPP was defined as a diagnosis of pneumonia with one or more positive blood cultures for S. pneumoniae. Identification of patients with BPP: one of the authors of this manuscript, (CH or JG), or a resident, reviewed admissions to the hospital daily, including holidays. The laboratory informed as soon as possible, when S. pneumoniae was isolated from blood culture. Data of chart was reviewed and a form was completed within 48-72h of admission. All patients were questioned, examined and followed exclusively by the authors. (JG or CH). When a patient with criteria of BPP was not admitted and sent home we strived to contact him in order to assist and include him in the study. Hospital based incidence was calculated dividing number of BPP/adult patients admitted annually to the hospital x 1000. Seasonal distribution was registered. Population incidence, was calculated during the period 20102015, adding to our series of patients with BPP admitted to the other two centres of the city, and considering population variations in the period. The following variables were recorded on admission directly from the subject, or from documentation in chart or interview with relatives: age, sex, duration of illness before consult, underlying chronic conditions such as diabetes, chronic renal failure, congestive heart failure, chronic lung disease, neurologic disease, malignancies, HIV infection, alcoholism, hepatic disease, smoking, prior antimicrobial therapy as well as clinical signs and symptoms. Living in nursing home or homelessness was registered too. Patients with dull percussion and bronchial breathing sounds on auscultation were considered as having clinical consolidation. Hypotension was defined as systolic arterial tension below 90mmHg. Abdominal pain, vomiting, hypotension, and confusion were considered nonpulmonary symptoms. Classical pneumococcal infection was considered if patients had all four of the following features: fever, pleuritic chest pain, lobar consolidation on chest X ray and leucocytosis. Pleural fluid examination was performed in all patients with pleural effusion. Empyema was considered when macroscopic pus or bacteria were identified in pleural fluid. History of pneumococcal vaccination was recorded in all cases and considered positive in patients who had received at least a single dose of 23-valent pneumococcal polysaccharide vaccine within the last 5 years. On admission, patients were stratified into risk classes I to V based on Pneumonia Severity Index (PSI) score [6]. Laboratory Leukocytosis was considered when white blood cells were more than 12,000/ml and leukopenia when WBC <4,000/ml Microbiological Testing S. pneumoniae was identified using standard microbiology procedures. One set of blood cultures were collected from each patient at entry, which is considered standard of care for patients with CAP admitted to the hospital. Conventional broth culture using nutritionally enriched media was used until 1997, after which fully automated, continuous blood culture monitoring equipment (BacT/ALERT® 3D BioMérieux, Inc. 100 Rodolphe Street, Durham, NC) became available. High quality sputum specimens (containing <10 squamous epithelial cells and >25 Polymorph Nuclear cells per low power field) were processed for bacterial diagnosis. Briefly, sputum was homogenized in 1.2 ml of sterile saline, spread onto a glass slide, air dried and heat fixed. Strains were identified based on Gram stains and morphology: gram-positive cocci found in singles, in pairs or in short chains were indicative of pneumococci infection. Sputum samples were inoculated on blood agar and chocolate agar plates and incubated at 35oC with 5-10% CO2 for 72 hours. All S. pneumoniae isolates were tested for penicillin susceptibility by diffusion, using 1 μg oxacillin disks and by broth micro-dilution test. Isolates were also screened for susceptibility to erythromycin, tetracycline, and levofloxacin using disk diffusion method. In addition, minimum inhibitory concentration (MIC) tests were used to determine susceptibility to erythromycin, extended spectrum cephalosporins, fluoroquinolones, tetracycline, trimethoprim sulfametoxazol, clindamycin, cefuroxime and vancomycin, in accordance to Clinical and Laboratory Standards Institute (CLSI, 2012) established guidelines [7]. Radiology Images on chest radiograph were classified by one of the investigators (JG) according to pattern (lobar consolidation, interstitial infiltrate, bronchopneumonia, pleural effusion) and extension (number of lobes affected, bilateral involvement) Outcome Patient were followed for 30 days after diagnosis, and complications were recorded, namely: pleural effusion, empyema, admission to ICU and need of mechanical ventilation. Overall case fatality rate was defined as death due to any cause within 30 days of hospitalization. Overall case fatality rate was defined as death due to any cause within 30 days of hospitalization. Statistical Analysis Qualitative variables are presented as the mean and range(minmax), while categorical variables are presented as frequency and percent. Contingency tables were used to measure associations with calculation of the chi-squared or Fisher’s exact test, and odds ratio (OR) were estimated. Multiple logistic regression analyses was performed to evaluate those factors found to be significant by univariate analysis and previously hypothesized to affect mortality. Two-tailed p-values are reported, with statistical significance when p<0.05. SAS V9.3 statistical software was used for calculations (SAS, Institute Inc. Cary, NC, USA). 48 ULJRI Vol 2, (1) 2018
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