Copyright ©ERS Journals Ltd 2003 Community-acquired pneumonia in the elderly: Spanish multicentre study1 Servicio de Neumología, Hospital de Cruces, Bilbao, 2 Servei de Pneumología i Allèrgia Respiratoria, Institut Clínic de Pneumologia i Cirurgía Torácica, Hospital Clinic, Barcelona, 3 Unidad de Cuidados Intensivos Respiratorios, Hospital Clínico, Valencia, 4 Servicio de Neumología, Hospital La Princesa, Madrid, 5 Sección de Neumología, Hospital Mutua Terrassa, Barcelona, 6 Servicio de Neumología, Hospital La Fé, Valencia, 7 Servicio de Neumología, Hospital Dr Peset, Valencia, and 8 Sección de Neumología, Hospital San Jorge, Huesca, Spain CORRESPONDENCE: TorresR. Zalacain, Secretaría SEPAR (Area TIR), Balmes 68 Pral, 08007, Barcelona, Spain. Fax: 34 934878509. E-mail: ssepar@separ.es Keywords: aetiology, clinical characteristics, community-acquired pneumonia, elderly, prognostic factors
Received: July 17, 2002
This study was sponsored by the "Area de Tuberculosis e Infecciones Respiratorias (TIR)", Sociedad Española de Neumología y Cirugía Torácica (SEPAR) and Aventis.
Community-acquired pneumonia (CAP) in the elderly has increased as a consequence of an overall increase of the elderly population. A controversy about the aetiology and outcome of CAP in this population still exists and more epidemiological studies are needed.
A prospective, 12-month, multicentre study was carried out to assess the clinical characteristics, aetiology, evolution and prognostic factors of elderly patients (
The clinical picture lasted The results of this study may aid in the management of empiric antibiotic treatment in elderly patients with community-acquired pneumonia and the patients who have a greater probability of bad evolution may be identified based on the risk factors. Community-acquired pneumonia (CAP) is a relatively frequent infectious disease with an incidence that ranges from 36 cases per 1,000 inhabitants per year 1. This incidence is markedly greater in elderly patients ( 65 yrs,) ranging from 2540 cases per 1,000 inhabitants per year 2. CAP also has greater morbidity and mortality in the elderly population than in a younger population, although apart from age, the association of underlying diseases, a very common associated factor in the elderly, accounts in part for this increased morbid-mortality 3, 4. Classically, the clinical presentation of CAP in the elderly has been described as quite subtle 5, 6, thereby leading to a delay in diagnosis and treatment. However, in some reports 7, 8 the clinical picture has been fundamentally acute with few variations with respect to younger patients. Although it is clear that Streptococcus pneumoniae is the most common aetiological agent, there are discrepancies in different studies regarding the true incidence of Gram-negative bacilli and Pseudomonas aeruginosa 5, 814. Mortality also appears to be increased in this group of patients with CAP, with values ranging 1535% 15 and there are few reports on the prognostic factors associated with the evolution of this disease 8, 11, 13. However, importantly, most reports dealing specifically with elderly patients with CAP have included a relatively low number of cases.
Since the number of elderly persons in Spain represents an important population,
Patients A total of 503 consecutive patients, 65 yrs in age, admitted to 16 Spanish hospitals for CAP from January 1 1997 to December 31 1997, were studied prospectively. CAP was defined when a new radiological infiltrate was identified with one of the major criteria or two of the minor criteria, as described previously 17, at the time of admission. The major criteria included cough, expectoration or fever ( 37.8°C); and the minor criteria included dyspnoea, pleuritic pain, altered mental status, pulmonary consolidation on auscultation and leukocytosis >12x109·L1. Patients were hospitalised according to the previously published recommendations of the Spanish Society of Pneumology 18. The following patients were excluded from the study: those who had been previously admitted within the last month, immunosuppressed patients, those with acquired immunodeficiency syndrome or patients receiving chemotherapy or corticosteroids (equivalent doses of prednisone 20 mg·day1). Patients with clinical confirmation of an alternative diagnosis other than pneumonia were also excluded from the study. The patients were examined within the first 24 h of hospital arrival, as well as throughout hospital stay. The diagnostic methods used and the treatment administered depended on the attending physician. At 40 days a follow-up visit with clinical and radiological control and serological analysis (when possible) was carried out.
Microbiology Sputum, pleural fluid, TAP and BPSB samples were cultured in the following medium: blood agar, chocolate agar, Sabouraud agar, buffered charcoal yeast extract, thioglycolate broth and medium for anaerobes of the Center for Disease Control.
The aetiology of pneumonia was considered as definitive under the following conditions: 1) isolation of a pathogen in cultures of blood or pleural fluid; 2) four-fold increase in IgG titres with final titres for C. pneumoniae (IgG Valid samples of sputum growing a predominant microorganism were considered for a very probable bacteriological diagnosis 19.
Data collection The data prior to admission included the following variables: age, sex, place of residence, grade of physical activity, bed confinement, smoking habits and alcohol consumption, swallowing disorders, number and type of associated diseases and previous antibiotic treatment. At the time of admission the following variables were collected prospectively: duration of symptoms prior to diagnosis, clinical symptoms (chills, cough, expectoration and its type, pleuritic pain, dyspnoea, alteration in mental state, arthromyalgias), exploratory data (body temperature, presence of crepitations or consolidation on auscultation, respiratory rate, cardiac frequency, mean blood pressure), analytical data (leukocyte count, haematocrit, haemoglobin, platelet counts, creatinine, glucose, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, proteins, albumin values and arterial pH, oxygen tension in arterial blood (Pa,O2), carbon dioxide tension in arterial blood and the Pa,O2/inspiratory oxygen fraction (FI,O2) ratio), radiographical data (number of lobes involved and type of consolidation, e.g. lobar, bronchopneumonia, segmentary (less than one lobe), bilateral involvement). During the evolution of the disease the following variables were collected: admission to intensive care unit (ICU), shock, need for mechanical ventilation, development of renal failure, radiographic progression, empyema, cavitation, modification in empiric antibiotic treatment, length of hospital stay, length of antibiotic treatment and death.
Other definitions
Statistical analysis
General characteristics and underlying diseases From January 1 1997 to December 31 1997, 503 elderly patients with CAP admitted to 16 Spanish hospitals were studied. The general characteristics and underlying diseases of these patients are shown in table 1 80 yrs of age. A total of 329 (65%) showed good physical activity established by the Karnofsky index 80. A further 430 (85%) had one or more underlying disease and 127 (25%) had received some antibiotic treatment prior to hospital admission.
Clinical data The main clinical data on hospital admission are shown in table 2 5 days in 318 cases (63%). The mean period of the clinical picture was 5.8±5.4 days. Overall the most frequent symptoms were cough (407 cases (81%)) and dyspnoea (351 patients (70%)). Fever ( 38°C) was observed in 380 patients (76%). The association of cough, expectoration and pleural pain (typical clinical picture) was seen in 152 cases (30%). An acute altered mental status was established in 26% of patients (130). No significant differences were found in any of the variables studied when patients were stratified according to age, sex, nursing home, prior physical activity or comorbidities (table 3 15x109 L1. The mean creatinine value on admission was 1.9 mg·dL1, with 141 cases (28%) showing values 1.4 mg·dL1. With regards to chest radiography, the infiltrate was predominantly alveolar, lobar (267 cases (53%)) or segmentary (118 (23%)).
Microbiological data Microbiological diagnosis was achieved in 199 cases (40%), being definitive in 164 (33%) and presumptive (with positive sputum culture as single sample) in 35 (7%). A total of 223 microorganisms were isolated and these are shown in table 5
Treatment of pneumonia The mean length of antibiotic treatment administered was 14.6±7.1 days. The antibiotics administered were as follows: third-generation cephalosporins in 279 patients (55%), macrolides in 222 (44%), aminopenicillins in 138 (27%), second-generation cephalosporins in 61 (12%), quinolones (ciprofloxacin) in 13 (3%), aminoglycosides in 11 (2%), clindamycin in 10 (2%) and others in seven patients (1%). Cephalosporin or aminopenicillin with a macrolide was given in 198 cases (39%). Monotherapy was administered in 264 (52%) patients as follows: third-generation cephalosporins in 151 (30%), aminopenicillins in 92 (18%), second-generation cephalosporins in 16 (3%) and macrolides in 5 (1%). Antibiotic treatment was modified in 126 cases (25%); in 61 (12%) due to aetiological findings (in 23 (5%) a microorganism which was not covered was observed and in 38 (30%) treatment was simplified). The total rate of failure to empirical treatment was 49 of 503 (10%). In 16 patients (3%) antibiotics were modified because of intolerance. The resistence of S. pneumoniae to penicillin was observed in 28 of 98 (29%), with 12 (12%) cases of intermediate resistance and 16 cases (16%) of high-level resistance. There were no differences when comparing sensitive to resistant cases and the presence or absence of prior antibiotic treatment, seven (10%) versus three (11%). Macrolides were only tested in 70 cases, showing resistances in 17 of them (24%) (four of them (25%) previously treated with antibiotics).
Evolution Mortality was not different when different antibiotic treatments were analysed. When cephalosporins or aminopenicillins were given with macrolides, mortality was 12%, with third-generation cephalosporins in monotherapy 9%, with aminopenicillins 12%, with second-generation cephalosporins 6%, with other associations 10% and with macrolides in monotherapy 0%, although only five patients received this type of monotherapy. The mean length of hospital stay was 11.2±7.8 days. Thirty-eight patients (8%) were admitted to the ICU, 13 of whom died (34%), and 21 (4%) required mechanical ventilation, nine of whom died (43%). The complications evaluated were as follows: renal failure (66 cases, 13%), shock (41 cases, 8%), empyema (14 cases, 3%) and disseminated intravascular coagulation (two patients, 0.4%).
Prognostic factors
Table 7 1.4 mg·dL1 at the time of admission and the existence of shock or renal failure during disease evolution were independent risk factors associated with greater mortality. Conversely, the existence of chills and a Pa,O2/FI,O2 ratio 200 were independent protective factors associated with a better prognosis.
This study is one of the largest series of elderly patients with CAP in the literature. The main findings were as follows: 1) contrary to common ideas, the clinical picture was acute ( 5 days) in 63% of the cases and that the main clinical respiratory data were present frequently ( 60% of the cases); 2) S. pneumoniae was the main aetiological agent observed, followed by H. influenzae and L. pneumophila. Some cases of Gram-negative enteric bacilli were also observed; 3) the mortality was relatively low, 11%. Although several prognosis factors were identified, neither age nor comorbidity were factors of poor prognosis on multivariate analysis.
CAP is common among the elderly population, with an increasingly higher incidence due to the progressive aging of the population. In the current study, including 503 patients, the mean age was 76.3 yrs, 85% of the cases presented a chronic underlying disease and only 30 (6%) of patients resided in a nursing home. These figures are very similar to those recently published in the USA, which studied 623,718 CAP patients The form of presentation of CAP in the elderly has been described classically as quite unspecific and subacute, with an absence of respiratory symptoms, fever in 4060% of the cases and a characteristic alteration in mental state in 2050% of patients 3, 5, 6, 9, 26. Although this is the prerecognised presentation, in the current study it was found that the main respiratory symptoms were found in >60% of cases with a previous clinical picture of <5 days in 63% and with 76% presenting fever. These data show a similar pattern to that found in studies considering younger patients 19, 27, although it must be noted that in 26% of this elderly population the characteristic alteration in mental state was present on admission. Thorax radiography in the present series demonstrated a predominance of lobar and segmentary infiltrates in 77% of the cases, which is very similar to that found in younger patients 28. Interestingly and in contrast to common ideas, no clinical differences were found in relation to other factors that could modify the clinical presentation. These factors were age (6579 yrs and >80 yrs), nursing home, prior physical activity and the presence of comorbidities. The present findings have been confirmed in at least two other series 7, 8, in which 77% and 56% of the cases, respectively, presented clinical manifestations that may be considered as typical. Moreover, in a comparative study 29 on clinical data in patients with bacteraemic pneumococcic pneumonia there were very few differences in these data between elderly patients and those <65 yrs. S. pneumoniae was by far the microorganism most frequently found, being observed in 49% of the cases diagnosed, followed by H. influenzae and L. Pneumophila. These findings are in agreement with other series, although with a notably lower number of cases included 5, 8, 11, 13. At the time of these previous studies in Spain the antipneumococcal vaccine was not routinely administered to the elderly population, and thus, this could explain the high incidence of S. pneumoniae in the present series. In addition no relationship could be found between S. pneumoniae resistant to antibiotics and the presence of prior antibiotic treatment and mortality. In the present series the high number of atypical microorganisms found (C. pneumoniae, M. pneumoniae, C. burnetii,) is also of note. This supports the finding of 32% of atypical microorganisms found in another study in Spain 11 and challenges the idea that atypical microorganisms are infrequent in old patients with CAP 5, 10, 12. In the current series, in which serology was almost systematically used, these pathogens represented 20% of the microbiological diagnoses. Conversely, the presence of other Gram-negative bacilli was found in 12% of cases. It has also been described previously that these pathogens may cause 1030% of the CAP in the elderly 3, 10, 12, although in other series 8, 11 this proportion did not surpass 3%, and in one series on severe CAP in the elderly admitted to the ICU 13 these microorganisms represented 16%. It is possible, at least in the present study, that a relatively low number of cases of Gram-negative bacilli may be due to the low number of patients from nursing homes where the number of these cases is usually greater 15, 27. Although treatment was not protocolised, the patients were mainly treated with third-generation cephalosporins or aminopenicillins with ß-lactamase inhibitors, associated or not with macrolides. This policy is the same as recommended in several guidelines of CAP 1, 18, 30. Antibiotic treatment was modified in 25% of the cases, but it should be noted that the change was only due to an uncovered bacteriological finding, therapeutic failure or intolerance in 88 cases (17%). Thus, the current authors agree with empirical antibiotic used, as described in the present study. Using this strategy this study covered most of the microorganisms causing CAP in this series, including S. pneumoniae resistant to penicillin. P. aeruginosa was not an important problem in the current series, and the authors believe that antipseudomonal antibiotics do not have to be administered as a routine initial option in this population. Moreover, the modification of the antibiotic therapy was not associated with a poor prognosis. In addition, no differences in mortality were found when comparing patients treated with ß-lactams alone or in combination with macrolides.
The mortality in the present study was relatively low (11%), especially if compared with other studies in which mortality ranged from 1535% 5, 8, 11. However, a recent study in the USA in a similar population showed a mortality of 11% 25. In the present series the prognostic score described by Fine et al. 30 was not used because the study was designed and initiated before its publication. The criteria of hospital admission used were those published in the guidelines of the Spanish Society of Pneumology 18. Accordingly, 85% of the patients had at least one comorbidity, increased mean values of respiratory rate, frequently altered renal function and in 26% of cases presenting an altered mental state. All these factors are indicators of the severity of the population reported here. It is possible that given the high presence of an acute clinical picture with fever and respiratory symptoms the diagnosis of pneumonia was not delayed and thus, treatment was rapidly initiated, thereby influencing the low number of complications observed and the relatively low mortality rate. The search for prognostic factors has been debated in different studies on CAP, but few reports have referred to elderly patients alone 8, 11, 13. Previous bed confinement was identified as a prognostic factor, as was identified by Riquelme et al. 11, which reflects the poor basal situation of the patient. The absence of chills and altered mental state was also found, demonstrating the presentation of unspecific pneumonia 3, 26, which could lead to a delay in diagnosis and treatment. Other factors were creatinine values In summary, the main clinical and aetiological characteristics and the evolution and prognostic factors of a large group of elderly patients with community-acquired pneumonia have been described here.
The authors would like to thank J. Vila from the Institut Municipal d'Investigació Médica (IMIM) de Barcelona, Barcelona, Spain, for his advice in the design of the statistical analysis and M. Niedermam from the Winthrop University Hospital, Mineola, NY, USA, for the critical review of the manuscript. Hospitals and physicians participating in the study: 1) Hospital de Cruces, Vizcaya (R. Zalacain and V. Cabriada); 2) Hospital Clínico, Valencia (J. Blanquer and D. Pérez); 3) Hospital la Princesa, Madrid (J. Aspa and B. Nieto); 4) Hospital Clínic, Barcelona (R. Celis and A. Torres); 5) Hospital Mutua Terrassa, Barcelona (L. Esteban); 6) Hospital La Fé, Valencia (R. Menéndez); 7) Hospital Dr Peset, Valencia (R. Blanquer); 8) Hospital San Jorge, Huesca (L. Borderías); 9) Hospital Central de Asturias, Oviedo (L. Molinos); 10) Hospital de Galdakao, Vizcaya (P.P. España); 11) Hospital Arnau Vilanova, Valencia (J.A. Pérez); 12) Hospital San Millán, Logroño (M. Barrón); 13) Hospital de Xativa, Valencia (J.M. Querol); 14) Hospital Universitario, Tenerife (R. Fernández); 15) Hospital Miguel Server, Zaragoza (S. Bello); and 16) Hospital General, Albacete (M. Arévalo).
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