Community-Acquired Pneumonia

Introduction Pneumonia constitutes the sixth cause of death and the first cause of infectious deaths in the United States (5). The incidence of pneumonia in community studies ranges from 2.6 to 16.8 per 1,000 adults per year (1,7,24,30,55). Most information and recommendations for clinical practice are based on studies of hospitalized patients, who represent only 5%-16% of pneumonia cases (24,39). Only 11 clinical studies of community pneumonia have been performed in ambulatory practice (1,9,10,16,17,23,36,38,42,51,55). Most of these studies have focused on etiology and provide little information about clinical outcome (9,16,42,51). In addition, interpretation of the results is hampered by the small number of patients (9,16,51), by incomplete microbiologic documentation (17,23,38,42), and especially by the absence of clear radiographic criteria (16,36,42,51,55). Understanding the outcome of community pneumonia is important because it allows physicians to evaluate the risk for potential complications and the natural history of symptom resolution. Few reports have assessed the prognosis of community-acquired pneumonia, especially in the ambulatory setting (13,22,23). The purpose of this prospective study is to establish the etiology, clinical and radiographic characteristics, and prognosis of community pneumonia in a population of patients seeking care from practitioners on an ambulatory basis. Patients and Methods Potential patients were recruited consecutively during ambulatory consultation by 11 practitioners. The inclusion criteria were as follows: 1) age over 15 years, 2) presence of recent symptoms of lower respiratory infection, 3) presence of pulmonary infiltrate on chest X-rays, and 4) patient’s consent. Patients coming from a nursing home or hospitalized during the month before the consultation were excluded from the study. The total number of patient visits during the period of the study was recorded by 5 practitioners. Patients Case history data were recorded in a standard questionnaire for each patient, comprising age, sex, occupation, comorbidities requiring regular medical follow-up and/or chronic medication (chronic obstructive pulmonary disease, heart failure, alcoholism, diabetes mellitus) and other relevant information. The following paraclinical exams were obtained: chest X-ray, differential blood count, virus cultures from a throat swab placed in a viral transport medium (0.2 M sucrose-phosphate containing 1% bovine serum albumin, 0.1 mg gentamicin per mL, and 2.5 mg amphotericin per mL), and serum samples at 0 and 4 weeks. Sputum sample for direct examination and culture and blood cultures were obtained before the initiation of antimicrobial therapy. The patients were treated with a macrolide antibiotic, josamycin with a loading dose of 1 g followed by 500 mg twice daily for 8 days or longer if infection with Legionella or Mycoplasma was diagnosed or suspected. The patients were followed up by the same practitioner, and seen at least once after 4 weeks. Symptoms and signs present during these consultations (feeling unwell, shivering, dyspnea, cough, expectoration, pleurodynia, headache, myalgia) were noted on a standard form and evaluated on a severity scale (1 = mild, 2 = moderate, 3 = severe). A chest X-ray was obtained at the first consultation and at least once more during a later consultation. Radiographic interpretation X-rays obtained for each patient were evaluated by a radiologist according to predefined criteria including the localization of the infiltrate (6 predefined zones: upper, middle and lower parts on the left and right lungs), and the presence of adenopathy, pleural reaction, or abscess formation. The pattern of infiltrates was categorized as predominantly alveolar, predominantly interstitial, or mixed alveolar and interstitial (53). Any other particular finding was also recorded, such as suspicion of tumor. The radiologic outcome was classified into 4 categories: 1) complete cure, 2) presence of minimal residual infiltrate, 3) improvement but significant residual lesion, or 4) no change or deterioration. Microbiology The serum specimens collected at 0 and 4 weeks were tested for antibodies by the following methods: standard complement fixation tests were used for Mycoplasma pneumoniae, Chlamydia spp., Coxiella burnetii, influenza viruses A and B, parainfluenza viruses types 1–3, adenoviruses, and respiratory syncytial virus. Indirect immunofluorescent antibody tests were used for Coxiella burnetii and L. pneumophila of serogroups 1–10. Chlamydia pneumoniae antibodies were tested by microimmunofluorescence (32). ELISA test was used to detect antibodies against Streptococcus pneumoniae. Sputum specimens were smeared for Gram stain and streaked on blood agar, chocolate, and MacConkey plates by the practitioner and incubated immediately at 37 °C. After a minimum of 12 hours, slides, agar plates, and the rest of the original specimen kept at 4 °C were sent to the reference laboratory by express mail. Gram stain was assessed in 3 different conditions: slide prepared and read by the practitioner, slide prepared by the practitioner but read by the microbiologist, and slide prepared with the original specimen and read by the microbiologist. A sputum was considered to be of good quality if it contained less than 25 epithelial cells per high power field (54). Pneumococcal antigen was also tested in the sputum. Definition of the etiologic diagnosis The etiologic diagnosis was considered as definite if there was a blood culture positive for a respiratory pathogen, a throat culture positive for a viral respiratory pathogen, or a fourfold or greater increase of serum antibody titers between the 2 samples obtained 4 weeks apart. The diagnosis was considered presumptive if there was a positive sputum culture for a respiratory pathogen or a high antibody titer on the initial specimen in a patient symptomatic for more than a week. For S. pneumoniae a positive pneumococcal antigen test in the sputum associated with a Gram stain showing Gram-positive diplococci was also considered as presumptive. When a patient met the criteria for a pneumonia due to 2 pathogens, the pathogen associated with a definite diagnosis was considered as dominant over the presumptive pathogen. For influenza A and B, high titers were accepted as evidence of recent infection only if the patient was not vaccinated and if the episode was compatible with the epidemiology. For most analyses, etiologic agents were grouped as follows: “pyogenic bacteria” (S. pneumoniae and Haemophilus influenzae), “atypical bacteria” (Mycoplasma pneumoniae, Chlamydia spp., Coxiella burnetii, and Legionella), “virus,” and “undetermined.” Statistical analysis Testing procedures for differences between specific groups included chi-square for categorical variables and the Student t- test or ANOVA for continuous variables. Associations were considered to be statistically significant if the p value was < 0.05 using a 2-tailed test. A Gram stain was considered as a true positive or negative when putting the patient in the correct etiologic category. Conversely, a Gram stain was considered as a false negative or a false positive when putting the patient in the wrong etiologic category. The sensitivity, specificity, negative predictive value, and positive predictive value were derived from this classification. Sensitivity and specificity of the 3 different Gram stain interpretations (slide prepared and read by the physician, slide prepared by the physician but read by the microbiologist, and slide prepared and read by the microbiologist) were compared in 3 different 2 × 2 tables of true positives, true negatives, false positives, and false negatives. The final etiologic diagnosis was used as reference standard. Results During the 4 years of the study, the 11 practitioners enrolled 184 patients, of whom 14 were excluded from analysis due to incomplete data or absence of pulmonary infiltrates on the chest X-ray upon review by the radiologist. This represented approximately 0.6 case per 1,000 patient visits. Etiology One-hundred seven etiologic agents were identified in 92 patients (54.1%) (Table 1). Evidence of bacterial infection due to pneumococci (34 cases) or H. influenzae (3 cases) was observed in 37 cases, “atypical” bacterial infection in 37 cases, and viral infection in 18 cases. The diagnosis was considered as definite in 44 cases and as presumptive in 48 cases. The most common organism was S. pneumoniae, followed by M. pneumoniae, influenza A virus, and C. pneumoniae (see Table 1). Polymicrobial infection was observed in 15 cases (11%).TABLE 1: Etiology in 170 patients with community-acquired pneumoniaAmong the 34 S. pneumoniae infections, the diagnosis was based on only 1 diagnostic test in 25 cases and on at least 2 diagnostic tests in 9 cases (Figure 1). The diagnosis was considered definite in 6 cases with positive blood cultures, and presumptive in the others. Since serologic tests could be performed in only 108 patients because of lack of available serum, the number of pneumonia episodes due to this organism may have been underestimated. S. pneumoniae was combined with another pathogen in 10 cases (virus, 6 cases; atypical pathogen, 4 cases). No blood cultures were positive for an organism other than S. pneumoniae. All 3 cases of H. influenzae pneumonia were diagnosed by sputum culture and Gram strain.Fig. 1: Positive diagnostic procedures in 34 cases of pneumonia due to Streptococcus pneumoniae.All “atypical” pneumonia episodes were diagnosed by serologic tests. Among 23 M. pneumoniae pneumonias, 21 were considered definite. M. pneumoniae was combined with another pathogen in 5 cases:S. pneumoniae (1 case), adenovirus (1 case), influenza B virus (1 case), parainfluenza virus (1 case), and beta-hemolytic Streptococcus (1 case). Pneumonia due to Chlamydia pneumoniae was diagnosed in 9 cases, of which 5 were considered definite and 4 presumptive. Pneumonia due to Coxiella burnetii was diagnosed in 4 cases (2 certain, 2 presumptive), and due to Legionella spp., in only 1 case. All viral cultures of throat swabs were negative in the first 100 patients, and the method was abandoned. The 18 cases of viral pneumonia were diagnosed by serologic tests. Among the 16 pneumonia cases due to influenza A or B virus, 7 diagnoses were considered definite and 9 presumptive. Among these 16 patients, evidence of superinfection by S. pneumoniae was observed in 5 cases. Pneumonia due to parainfluenza virus and adenovirus was diagnosed in 1 case each. Sex and age Among the 170 patients analyzed, 82 (48.2%) were men. Median age was 43.1 years (range, 15–96 yr) (Table 2). Seventy percent of the patients had no comorbidity. The most common underlying conditions observed in the remaining patients were cardiac disease (10.6%), chronic obstructive pulmonary disease (6.5%), and diabetes (2.9%); 35.3% of the patients were smokers and 12.9% were alcoholics.TABLE 2: Underlying conditions according to etiologic categoriesThe median age of patients suffering from bacterial or viral pneumonia was significantly higher than that of patients presenting with atypical pneumonia (see Table 2). S. pneumoniae caused 28.2% of pneumonias in patients over 45 years, and 13.0% in younger patients (p = 0.01). All 3 H. influenzae episodes were observed in patients over 45 years. M. pneumoniae was responsible for of pneumonias in patients 45 years and in patients over that age (p < C. pneumoniae for of pneumonias in patients 45 years, compared with only in patients (p = (Figure 2: Etiology in 170 with pneumonia by age in were more in patients with viral pneumonia and less in patients suffering from atypical pneumonias (see Table 2). No patients with cardiac with pneumonia due to M. pneumoniae, this pathogen caused of pneumonias in the other patients (p = A virus caused of episodes patients with cardiac and of episodes in patients heart disease (p = No significant was observed in the etiology of pneumonia in to the presence or absence of chronic obstructive pulmonary disease, or Among 7 patients vaccinated against S. pneumoniae in the 5 years, 2 with pneumococcal Among 6 patients vaccinated against 2 pneumonia due to influenza A virus. The is in percent of pneumonias in in in in (p < Among the S. pneumoniae pneumonias, were diagnosed in (p = percent of pneumonias of in and (p < percent of pneumonias due to M. pneumoniae were diagnosed during the first 2 years of the study (p < and of cases due to influenza A virus, during the year (p = 0.01). pneumonias of the study, there was a in during the of pneumonia due to and influenza Etiology in 170 with pneumonia over 4 stain Sputum was obtained from patients (Table The and specificity of the sputum Gram stain to the final etiologic and were evaluated for 3 different When the slide prepared by the practitioner was read by of the were of but the and specificity to the etiologic diagnosis were When the same slide was by the reference laboratory microbiologist, only 37 were of but the and specificity were When the slide was prepared and read by the microbiologist, were of the was but the specificity was Sensitivity and specificity of the Gram stain according to 3 different signs and symptoms The symptoms most were and (Table The most common clinical were and (Table pneumonias were by pleural observed in the other etiologic and more and sputum (p = as as higher The was significantly less patients with atypical pneumonia (p < and of symptoms according to etiologic signs and laboratory according to etiologic chest X-rays were available for interpretation by the radiologist in cases, with follow-up X-rays for cases (Table The presence of an infiltrate was considered to be in of cases, and to be in 1% of cases cases were excluded from The infiltrates were predominantly in the left (p < especially the middle and lower infiltrates were observed in of cases. The infiltrate was alveolar in and interstitial in In of the episodes the infiltrate not a or adenopathy, or abscess were pneumonias were significantly associated with an interstitial infiltrate with and with a right median The infiltrate was more as alveolar in cases of “atypical” or bacterial pneumonia according to etiologic and outcome with josamycin was in of the 170 patients was at the of the in 12 cases, including 9 patients for whom was during the consultation and 3 patients for other In most patients the outcome was after 4 with of and other signs improvement of the chest X-ray and improvement of laboratory (see 5 and Patients with viral pneumonia not as as with other after the initiation of the median of and on was significantly and a complete radiologic at 4 weeks was observed in only of cases, a that is significantly lower than in the other etiologic groups (p = Among the patients treated with the was in 11 cases due to (1 or no improvement of symptoms after a days of cases). was diagnosed in 6 patients in in and in 1). The diagnosis was at the of the first consultation in 4 patients on the of the chest X-ray (3 cases) or of (1 case). In the other 2 cases, the diagnosis was on the of the chest X-ray, associated with clinical in 1 of In another 3 patients, a was on the chest X-ray but was not upon and A total of 14 patients in 9 of the was during the initial and in at a later due to to therapy. The median age of the hospitalized patients yr) was higher than that of the other patients yr) (p = and more with comorbidities p = especially with chronic obstructive pulmonary disease p = and p = 0.01). blood cultures were positive in 3 of the 14 hospitalized patients and in only 3 of the patients (p < The 2 groups not significantly with to against S. pneumoniae or with recent infection, or infection in patients had pneumonia of The first patient, years, was hospitalized for pneumonia and from due to The patient, years, at home a days after the diagnosis of pneumonia associated with heart This study identified 170 patients with community-acquired pneumonia diagnosed by practitioners at for the Pneumonia study only a of patients with lower respiratory in reports had chest X-rays performed and/or with an infiltrate the study was not to the cause of pneumonia, and the of patients with microbiologic documentation was In the present study, a of diagnostic tests were were for the diagnosis which were classified as or into the specificity of the tests. This for with other studies particular was to patient which included a at 4 weeks. The organism identified most was S. pneumoniae. In studies performed in hospitalized patients, S. pneumoniae is the most common etiologic up to of of pneumonia S. pneumoniae was also the organism most in community studies have atypical such as M. C. or viruses to be more may these In tests to pneumococcal pneumonia were not in the studies (Table In studies S. pneumoniae was at least 3 diagnostic were used blood test for pneumococcal antigen at The specificity of tests may also to of the number of pneumococcal of studies of pneumonia in pneumococcal antigen test of the sputum could be performed in patients diagnosed with pneumococcal pneumonia, and was positive in 10 A good between the of pneumococcal antigen in the sputum by and the in antibody titers in pneumonia patients that the of this antigen is a of infection than the and specificity of this test have not been evaluated In study only 3 of the 34 cases of pneumococcal pneumonia were diagnosed on the of this examination and the presence of diplococci on Gram that it could not have to an of the of pneumococcal pneumococcal pneumonias were diagnosed on the of a fourfold in antibody but the tests could be performed in only 108 of the 170 cases. cultures were positive for S. pneumoniae in 6 cases. Sputum cultures were positive in 11 cases, and 2 of the 34 pneumococcal pneumonias were diagnosed on the of this have that only of patients with pneumococcal pneumonia with have a positive sputum culture have that sputum cultures not be performed in less patients sensitivity, cultures to the of which be important in the of pneumococci with to common been noted in during the M. pneumoniae is the etiologic in of incidence and was responsible for of the This organism was the most common etiologic in 2 it represented of cases of pneumonia the other it was in other studies differences may be due to differences in diagnostic tests and lack of on diagnostic This may also be by and by years The present study this the M. pneumoniae in the first 2 years of the study. In C. pneumoniae caused up to of the episodes it was observed more in other studies (see Table used may for these differences In study, C. pneumoniae were in C. pneumoniae have been pneumonia was in of patients, and were to influenza viruses A or B superinfection in viral pneumonia is most caused by S. pneumoniae and S. pneumoniae and influenza A or B virus were in 5 of cases, but no due to pneumonia was seen most in patients presenting with especially heart were in of and types of were as by of diagnostic the of pneumonia of high in most from to In study, these episodes for of the episodes and that bacterial pneumonia in cases count, and atypical or viral pneumonia in other cases The of these episodes during of pneumonia due to Mycoplasma pneumoniae and influenza A virus. This that of the pneumonias of are caused by the same etiologic which may be This may be by the of the absence of sputum available for cultures or of serologic tests pneumonias of may be caused by In this are the in pneumonia, pulmonary and but in pneumonia not been that a of pneumonias of be due to In 2 studies were in and of patients presenting with community-acquired pneumonia, were only differences in the clinical of the different etiologic Patients with S. pneumoniae pneumonia with pleural and sputum significantly more and had higher have that the of of sputum and pleural to between the etiologic and that are higher in S. pneumoniae pneumonia This not been in studies have been associated with etiologic a analysis based on age, of the disease, sputum characteristics, count, and radiographic to patients grouped into 4 etiologic groups and placed only of cases in the correct The value of direct examination of sputum been for years. The to sputum Gram at least for hospitalized patients the not it at of including the count, epithelial and of have been for the quality of the but been to be to the (54). have that the presence of with of constitutes an for In a study performed at the in about the sputum specimens a pulmonary pathogen by direct and there was a between the identified by and identified by other studies have the of Gram stain Among 12 different studies on the of sputum Gram the from to and the specificity from to and results to the these the results were different in 3 different conditions of with different slide and different sputum specimens could be obtained in only of patients and were considered to be of good quality in only of The presence of a radiologic infiltrate was by the radiologist in of cases. In patients in the study, an infiltrate was by at least 2 of 3 in of cases was that the left was significantly more than the a finding which to not been pneumonias were significantly more by and interstitial The infiltrates were to a definite or the number of or the presence of studies have between radiographic and a etiologic these there are no radiologic criteria to an etiologic diagnosis the chest X-ray may be of analysis of the clinical and radiographic of patients that the presence of pleural is significantly associated with other studies performed in patients treated on an ambulatory most patients were but the of the according to the S. pneumoniae pneumonia was significantly more common patients, as as to M. pneumoniae and C. pneumoniae, the of other studies patients had a median age of years as compared to years for in addition, the of comorbidities was higher were in the study, in which heart and pulmonary were 4 and 2 more hospitalized patients, In another study of patients hospitalized for community pneumonia in the incidence of and conditions was these conditions were in In a was to be associated with the episodes in 6 cases Most patients in this study had a good the of the only of patients were and less than of signs of pneumonia on The clinical symptoms and radiologic infiltrates in patients with viral pneumonia longer than in the other etiologic 1 the was in of cases and the had from 37 to 7 Radiographic examination improvement or in of cases. are to of others. Among patients with community-acquired pneumonia, radiologic signs of improvement were observed in of the cases after 5 days of and residual radiographic signs in only after 4 weeks In the study, of with community-acquired pneumonia had to or during a 1 month of only 2 of 170 patients had over years and with This is to the study, in which only 6 of with community-acquired pneumonia of were as patients based on a for prognosis in pneumonia This is also with recent studies in a of and the patient population according to the setting of (see Table This with the of and in 2 studies of patients hospitalized for community-acquired The present study that pneumonia a outcome and be in an Patients hospitalized for community-acquired pneumonia only a small of patients with pneumonia, with different characteristics, including higher age and more and In a small of patients in this the pneumonia episode is the first of a a prospective study with a of practitioners to the etiology, clinical and outcome of community-acquired pneumonia in patients diagnosed in the All patients with signs and symptoms of pneumonia and an infiltrate on chest X-ray an standard and were followed over 4 weeks. a 184 patients were of whom 170 15–96 yr) were included and In no etiologic could be In the remaining 92 patients, etiologic agents were were due to Streptococcus pneumoniae, 3 Haemophilus spp., 1 Streptococcus were due to “atypical” Mycoplasma pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella and 25 were due to viruses influenza viruses and 5 other respiratory were only a statistically significant clinical differences between the different etiologic age and comorbidities in viral or in episodes of etiology, higher in more and interstitial infiltrates in viral were 2 in patients with age and years and Only 14 patients In 6 patients the pneumonia episode a This study that most cases of community-acquired pneumonia have a outcome and be in an in the absence of and clinical or laboratory tests to establish a definite etiologic diagnosis at the of the etiologic agents that initial S. pneumoniae and atypical as as influenza viruses during the