- Email: [email protected]
Study of community-acquired pneumonia: Incidence, patterns of care, and outcomes in primary and hospital care
Journal of Infection (2010) 61, 364e371
www.elsevierhealth.com/journals/jinf
Study of community-acquired pneumonia: Incidence, patterns of care, and outcomes in primary and hospital care* ˜a a, Amaia Bilbao b, Julio Gamazo c, Alberto Capelastegui a,*, Pedro P. Espan ˜aki Gorostiaga d, Cristobal Esteban a, Federico Medel d, Juan Salgado d, In Lander Altube a, Inmaculada Gorordo a, Jose M. Quintana e, on behalf of Poblational Study of Pneumonia (PSoP) Group a
Pneumology Service Hospital Galdakao, 48960 Galdakao, Bizkaia, Spain Basque Foundation for Health Innovation and Research (BIOEF) e CIBERESP, Sondika, Bizkaia, Spain c Emergency Service Hospital Galdakao, Galdakao, Bizkaia, Spain d General Practice Comarca Interior, Bizkaia, Spain e Research Unit Hospital Galdakao e CIBERESP, Galdakao, Bizkaia, Spain b
Accepted 5 July 2010 Available online 6 August 2010
KEYWORDS Pneumonia; Epidemiology; Management
Summary Background: To asses the incidence, patterns of care, and outcomes of community-acquired pneumonia (CAP) in the population of a defined geographic area. Methods: Prospective study conducted from April 1, 2006, to June 30, 2007. All adult patients (age 18) with CAP in the Comarca Interior region of northern Spain were identified through the region’s 150 family physicians and the emergency department (ED) of the area’s general teaching hospital. Results: During a 15-month period, 960 patients with CAP were identified: 418 hospitalized and 542 ambulatory patients. The hospitalization rate was 43.5% and the global 30-day mortality was 4% (38 patients). Of the patients treated at home, most (90.4%) had mild pneumonia, only 3.1% (17 patients) were subsequently hospitalized, with a 30-day mortality rate of 0%. However, 48.9% were not treated according to antibiotic recommendations of the Spanish Society of Pneumology. Mean duration of return to daily activity was 18.8 days for the entire population. The incidence study was restricted to the first 12 months, during which 787 patients
Abbreviations: AUC, area under the receiver operating characteristic curve; CI, confidence interval; CAP, community-acquired pneumonia; CURB-65, confusion, urea nitrogen, respiratory rate, blood pressure, age 65 years; CRB-65, confusion, respiratory rate, blood pressure, age 65 years; FP, family physician; ICU, intensive care unit; IDSA/ATS, Infectious Diseases Society of America/American Thoracic Society; ROC, receiver operating characteristic curve; SEPAR, Spanish Society of Pneumology. * Sources of support: Basque Health Care Service. * Corresponding author. Tel./fax: þ34 944007002. E-mail address: [email protected] (A. Capelastegui). 0163-4453/$36 ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2010.07.015
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fulfilled the inclusion criteria. This represented an incidence of pneumonia of 3.1/1000 adults per year. Both the incidence of CAP and hospitalization for it rose with age. Conclusions: Our study offers information about CAP in the general population and provides feedback for the management of CAP. Although the selection of patients to be treated at home was appropriate, the choice of empiric antibiotic therapy for ambulatory CAP was problematic. ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Background Community-acquired pneumonia (CAP) is a major cause of morbidity in the community. It requires numerous family physician (FP) visits each year as well as a substantial number of hospital admissions,1,2 and thus imposes great burdens on health services. Most studies of CAP have been based on selected series of hospitalized patients. However, 40e80% of adults with CAP are treated on an ambulatory basis,3e7 and little information is available about this population. True incidence data are essential for the development of rational prevention programs, the allocation of health care resources, and the identification of changes in disease patterns. The incidence of CAP reported in developed countries has ranged from 1.6/1000 to 16/1000 per year.3,4,6,8 Of the few population-based incidence studies reported, the populations assessed have been small (<100,000 inhabitants), and all of the studies were conducted at least 10 years ago. A study conducted in Denmark showed that incidence of pneumonia requiring hospitalization has increased by 50% from 1994 to 2004, with a persistent high mortality rate.9 It is possible that the pattern of adult CAP may be changing elsewhere, particularly in patients not admitted to hospital, given the promotion of fluoroquinolones for the treatment of CAP and the implementation of clinical prediction rule. Updated knowledge about the management of inpatients and outpatients with CAP may raise questions regarding the current care of patients with CAP and offer new strategies for treatment. However, although there have been several reports on adults with CAP admitted to hospital,10e12 there have been no recent, comprehensive population-based studies including outpatients treated by FPs as well as hospitalized patients. The objective of our study was to provide a contemporary assessment of the incidence, patterns of care, and outcomes of CAP in the population of a defined geographic area. To do so, we conducted a study of all cases of CAP in a population aged 18 years or older of our area during a 15month period.
Country.13 Health care in this region is provided by the public network of the Basque Health Care Service-Osakidetza, which provides free unrestricted care to nearly 100% of the population. The study was conducted from April 1, 2006, to June 30, 2007. Patients were recruited from a teaching hospital (Galdakao Hospital), the only hospital in the area, and 150 FPs working in the Comarca Interior region. We instituted an extensive information campaign among all FPs serving the study population to make practitioners aware of the study and ask them to alert us to patients with CAP. By study protocol, patients with suspected pneumonia underwent x-ray. All adult cases of confirmed pneumonia that occurred during the study period were prospectively and consecutively enrolled in the incidence study. A member of the research team checked all discharge diagnoses of hospitalized patients and added previously unidentified cases who fulfilled the criteria to the study population. All eligible participant patients were informed of the study goals and gave informed consent to participate in the study. The project was approved by the hospital’s ethics review board.
Definition of pneumonia Community-acquired pneumonia was defined as pulmonary infiltrate on chest radiograph not known to be old and symptoms consistent with pneumonia, including cough, dyspnea, fever, and/or pleuritic chest pain not acquired in a hospital or a nursing home residence. Patients were excluded if they were known to be positive for human immunodeficiency virus, were chronically immunosuppressed (defined as immunosuppression for solid organ transplantation, postsplenectomy, receiving 10 mg/day of prednisone or the equivalent for more than 30 days, treatment with other immunosuppressive agents, or neutropenia, i.e., <1.0 109/L neutrophils), or who had been discharged from an acute care hospital or an on-site subacute care unit or from palliative care within the previous 14 days. Cases were confirmed if there was a radiological finding suggestive of pneumonic infiltrate as reviewed by two members of the research team (PPE and AC).
Patients and methods Patient management Setting and study population The Comarca Interior region, situated in the Basque Country (northern Spain), has a mixed urban, suburban, and rural population of 300,299 (254,523 aged 18). The age distribution, education level, sources of employment, socioeconomic status, and health care services of the urban population are representative of the overall Basque
Management for patients who initially visited an FP was left to the FP’s discretion. Patients presenting to the emergency department of GaldakaoHospital during the study period were managed according to a clinical guideline.12 As part of the clinical guideline, after patients were discharged they were managed by their own FP, with a follow-up visit to the hospital within 30 days of discharge.
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Measurements and management evaluation Clinical and demographic characteristics of each patient were recorded, along with all of the variables for the CURB-65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, age 65 years) score14 within the first 24 h after diagnosis. Process-of-care variables included the therapy employed (recorded as initial choice of antibiotic treatment, whether or not it was consistent with recommendations of the Spanish Society of Pneumology (SEPAR)15 or the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines,16 and antibiotics taken prior to admission), and the duration of antibiotic therapy. Outcome measures included vital status at 30 days after diagnosis; in-hospital mortality; admission to the intensive care unit (ICU); need for mechanical ventilation; septic shock (defined as systolic arterial tension <90 mmHg and requirement of vasopressors for a minimum of 4 h);
Table 1
treatment failure (defined as the development of clinical deterioration with hemodynamic instability, demonstrated respiratory failure or the appearance of it, required mechanical ventilation, demonstrated radiographic progression of pneumonia or the appearance of a new infectious foci, or had persistent fever or the reappearance of fever if change in treatment was needed); severe sepsis defined as sepsis associated with organ dysfunction and perfusion abnormalities17; hospital readmission within 30 days; length of hospital stay (calculated as the discharge date minus the admission date); length of time needed to return to normal daily activities; and subsequent hospitalization for patients initially treated as outpatients. Vital status and readmission information for all patients were initially determined by telephone interviews up to 90 days after discharge. All reported deaths and dates of death were confirmed by a review of medical reports, public death registries, or both.
Demographic and clinical characteristics of patients with community-acquired pneumonia in northern Spain.
Characteristics Host related Age, years, mean (SD) Range 18e44 45e64 65e74 >74 Women Immunized against influenza Immunized against pneumococcal infection Underlying diseases Neoplastic disease Liver disease Congestive heart failure Cerebrovascular disease Renal disease Chronic obstructive pulmonary disease Diabetes mellitus Number of comorbid conditions 0 1 >1 Severity of illness in admission CURB-65 scorea 0e1 2 >2 CRB-65 scoreb 0 1 >1 Bilateral or multilobe radiographic involvement
All (N Z 960)
Inpatients (N Z 418)
Outpatients (N Z 542)
P value
60 (20.3)
71.7 (16.6)
50.9 (18.1)
<0.0001 <0.0001
272 (28.3) 231 (24.1) 157 (16.4) 300 (31.3) 389 (40.5) 377 (41.8) 45 (5.1)
44 (10.5) 57 (13.6) 84 (20.1) 233 (55.7) 149 (35.7) 245 (63.3) 34 (9.3)
228 (42.1) 174 (32.1) 73 (13.5) 67 (12.4) 240 (44.3) 132 (25.6) 11 (2.1)
34 (3.5) 12 (1.3) 29 (3) 38 (4) 30 (3.1) 115 (12.3) 101 (10.8)
25 (6) 7 (1.7) 23 (5.5) 33 (7.9) 22 (5.3) 83 (20.5) 71 (17.6)
9 (1.7) 5 (0.9) 6 (1.1) 5 (0.9) 8 (1.5) 32 (6) 30 (5.6)
660 (71) 198 (21.3) 71 (7.6)
214 (53.1) 132 (32.8) 57 (14.1)
446 (84.8) 66 (12.6) 14 (2.7)
670 (69.8) 193 (20.1) 97 (10.1)
180 (43.1) 145 (34.7) 93 (22.3)
490 (90.4) 48 (8.9) 4 (0.7)
449 383 128 111
71 (17) 230 (55) 117 (28) 99 (24.6)
378 (69.7) 153 (28.2) 11 (2) 12 (2.3)
0.007 <0.0001 <0.0001 0.0003 0.298 <0.0001 <0.0001 0.0008 <0.0001 <0.0001 <0.0001
<0.0001
<0.0001 (46.8) (39.9) (13.3) (12)
<0.0001
SD, standard deviation; Data are presented as numbers (percentage) unless otherwise stated. Percentages exclude patients with missing data. P value, between inpatients and outpatients. a Severity of illness on admission assessed with CURB-65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, age 65 years) score. b Severity of illness on admission assessed with CRB-65 (Confusion, Respiratory rate, Blood pressure, age 65 year) score.
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Chi-square and Fisher’s exact tests were performed for the comparison of categorical variables, and the Student t test and non-parametric Wilcoxon test were performed for continuous variables. The incidence analysis was restricted to a 12-month period (April 1, 2006 to April 1, 2007). The predictive accuracy of the CURB-65 and CRB-65 (the same as the CURB-65 but without the urea measurement) severity scores was determined by calculating the area under the receiver operating characteristic (ROC) curve.18 Area under the curve (AUC) values was compared using the non-parametric method described by Hanley and NcNeil.19 All effects were considered significant at P < 0.05. All statistical analyses were performed using SAS for Windows statistical software, version 9.2 (SAS Institute, Inc., Carey, NC).
Results
12
12
250
10
10
200
8
150
6
100
4
8 6 4
50
2
2
0
0
0
18-44
45-64
65-74
>74
Incidence of hospitalization (per 1 ,000 pop)
300
Incidence (per 1, 000 pop)
Number of cases
During a 15-month period, 960 patients with CAP fulfilled the inclusion criteria. Of these, 542 were initially treated on an outpatient basis and 418 were initially hospitalized for treatment. Only 13 (1.4%) of the patients were identified retrospectively from the hospital database; their demographic variables, coexisting conditions, and severity of CAP upon admission were similar to those of the hospitalized patients recruited prospectively. Characteristics of the entire study cohort are provided in Table 1. Compared with hospitalized patients, those treated on an outpatient basis were significantly younger, more likely to be female, had fewer comorbidities, and had a lower severity of CAP. Among the 542 patients managed on an outpatient basis, 269 (49.6%) were initially attended to and diagnosed by an FP, while 273 were initially attended to and diagnosed in the emergency department of Galdakao Hospital. Demographic variables, coexisting conditions, CAP severity upon admission, and outcomes were similar
Age (years)
for these two group with the exception of the prescription of antibioticsdpatients initially seen by an FP had the lowest use of quinolones and higher use of macrolides (p < 0.0001).
Community incidence of CAP A total of 787 patients who fulfilled the inclusion criteria from April 1, 2006 to April 1, 2007 were included in the incidence study. This represented an incidence of CAP of 3.1/1000 adults per year. The age-specific number of cases and incidence are shown in Fig. 1. The incidence rose more than five-fold with age from 1.7 per 1000 in those aged 18e44 years to 9.9 per 1000 in those aged 74 years and older. The incidence of hospitalized CAP in those 65 years or older was 4.9 cases per 1000 population. Pneumonia incidence rates were lower during the summer than during the winter and spring (p < 0.0001) (Fig. 2).
Management and outcomes We assessed the severity of illness at diagnosis using the CURB-65 and CRB-65 scores. A CURB-65 score 2 was 94.7% sensitive and 72.5% specific at predicting 30-day mortality (negative predictive value (NPV), 99.7%; positive predictive value (PPV), 12.4%), while a CRB-65 score 1 was 97.4% sensitive and 48.6% specific (NPV, 99.8%; PPV, 7.2%). The CURB-65 and CRB-65 scores performed equally well with regard to the prediction of 30-day mortality (AUC 0.90 versus 0.87, p Z 0.0501, Fig. 3). Antibiotics initially prescribed for CAP patients are shown in Table 2. Statistically significant differences were observed among inpatients and outpatients. Prescriptions for the treatment of CAP were, in rank order, a quinolone (58.5%), b-lactams (24%), macrolides (10.6%), and b-lactams/macrolides (5.8%). Almost half (48.9%) of ambulatory patients were not treated according to antibiotic recommendations of SEPAR. 140 120 100
No.of patients
Statistical analysis
18-44 years
80
45-64 years 65-74 years
60
>74 years
40 20 0
A 2006
Figure 1 Age-specific number of cases, incidence rate per 1000 inhabitants, and rate of hospitalization per 1000 inhabitants in patients with community-acquired pneumonia in northern Spain. Incidence of pneumonia (diamonds) and incidence of hospitalization (rectangles) rose with age across all age group (p < 0.0001). Bars Z Number of cases by age categories.
M
J
J
A
S
O
Months
N
D
J
F
M
2007
Figure 2 Age-specific number of cases of communityacquired pneumonia by month of diagnosis in patients with community-acquired pneumonia in northern Spain. Incidence rate per 1,000 inhabitants over the course of the year was 1.2 in winter, 0.8 in spring, 0.6 in summer, and 0.6 in autumn (p<0.0001).
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9.1% (38 cases) compared with 0% among those treated on an ambulatory basis. Morbidity was also low among ambulatory patients, with 17 (3.1%) requiring hospitalization d9 due to treatment failure, 3 for pleural effusion, 2 for respiratory insufficiency, 1 for a myocardial infarction, 1 for lung cancer, 1 for urticariad but with no deaths or ICU admissions. Mean duration of return to daily activity in the entire population was 18.8 days, with outpatients returning to daily activity 1.5 days sooner than inpatients (p Z 0.0007). For the 324 patients who were employed at the time of their CAP diagnosis, the period of sick leave was recorded for 274 (84.6%). Of these, 17 (6.2%) returned to work within one week, 34 (12.4%) within two weeks, and 242 (88.3%) within one month, while 32 (11.7%) were absent for longer than one month. The mean time away from work for all employed patients was 25.5 days, with outpatients returning 3.3 days sooner than inpatients (p Z 0.0004).
S e n s i t i vi t y
,75
,50
,25 ______ CURB65 (AUC = 0.90, 95%CI = 0.85 to 0.95) ____
0,00 0,00
,25
CRB65 (AUC = 0.87, 95%CI = 0.82 to 0.93)
,50
,75
1,00
Discussion
1 - Specificity
Figure 3 Receiver-operator-characteristic curves of predicting 30-day mortality according to CURB-65 and CRB-65 scores. AUCZarea under the curve; CIZconfidence interval. The CURB-65 and CRB-65 scores performed equally well with regard to the prediction of 30-day mortality (pZ0.0501).
The hospitalization rate was 43.5%. Among patients initially seen and diagnosed by an FP (269 cases), 97.4% were treated at home, compared to 39.5% (273 cases) of patients initially seen and diagnosed in the emergency department of Galdakao Hospital. The age-specific rates in admission, mortality, and hospitalization are shown in Fig. 4. Outcomes among inpatients and outpatients are shown in Table 3. The mortality rate among hospitalized patients was
Table 2
In this prospective study, we assessed the incidence, patterns of care, and clinical outcomes of CAP in the entire adult population of the Comarca Interior region of northern Spain. We confirmed the substantial burden of CAP, estimating an annual incidence of 3.1 cases per 1000 adults per year, a 42.8% rate of hospital admission, and a CAPinduced period of inactivity of almost 20 days. We observed that the management of hospitalized and ambulatory patients was generally effective, although the prescription of antibiotics for outpatients was often not in agreement with the recommendations of established guidelines. We also observed that patients selected for ambulatory treatment were appropriately identified, with 90.4% having mild pneumonia and CURB-65 scores generally <2. Both the CURB-65 and CRB-65 scores were good predictors of 30-day mortality (AUC 0.90 and AUC 0.87, respectively).
Process-of-care of patients with community-acquired pneumonia in northern Spain.
Process of care Antibiotics prescribed B-lactam Macrolide B-lactam/macrolide Fluoroquinolone Others Taking antibiotics prior to diagnosis Appropriate antibiotic therapy according Spanish guidelinesa Appropriate antibiotic therapy according American guidelinesa Antibiotics within 8 h Duration of antibiotic therapy after diagnosis, mean (SD), daysb Duration of intravenous therapy after diagnosis, mean (SD), daysb
All (N Z 960)
Inpatients (N Z 418)
Outpatients (N Z 542)
228 (24) 101 (10.6) 55 (5.8) 556 (58.5) 11 (1.2) 156 (17.3) 624 (65.6)
61 (14.6) 3 (0.7) 50 (12) 294 (70.5) 9 (2.2) 77 (20.3) 351 (84.2)
167 (31.3) 98 (18.4) 5 (0.9) 262 (49.1) 2 (0.4) 79 (15.1) 273 (51.1)
0.042 <0.0001
714 (75.1)
351 (84.2)
363 (68)
<0.0001
e 9.9 (2)
366 (89.3) 9.8 (2.2)
e 10 (1.8)
e 0.002
e
2.7 (2.4)
e
e
P value <0.0001
SD Z standard deviation; Data are presented as numbers (percentage) unless otherwise stated. Percentages exclude patients with missing data. P value, between inpatients and outpatients. a Appropriate antibiotic according Spanish guidelines (ref. 15). Appropriate antibiotic according U.S. guidelines (ref. 16). b In-hospital deaths are excluded.
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CURB65: 2
369
CURB65: >2
90
300
12
80
50
150
40 30
100
20
50
10 0
18-44
45-64
65-74
8 6 4
30 days mortality (%)
60
200
0
10
70 Hospitalization (%)
Number of cases
250
2 0
>74
Age (years)
Figure 4 Age-specific severity in admission, hospitalization and 30-day mortality in patients with community-acquired pneumonia in northern Spain. Hospitalization (diamonds) and mortality (rectangles) increased across all age groups (p < 0.0001). Bars Z number of cases according severity in admission measure by CURB-65 score.
Three truly community-based studies of pneumonia incidence were conducted in smaller populations in Finland (38,128 inhabitants aged 15),4 in Barcelona, Spain (74,368 inhabitants aged 14)6 and in Nottingham, England (53,137 inhabitants aged 15e79).3 The overall incidence of CAP was approximately 9/1000 in Finland, 1.6/1000 in Barcelona, and 4.7/1000 in Nottingham. In the United States, data from the National Health Interview Survey estimated the annual incidence of pneumonia for persons 18 years and older, including those treated in outpatient settings, at 16.3/1000 per year.8 Our study was based on a population of almost 300,000 adults, which is much larger than previous population-based studies. Our estimated annual incidence of 3.1/1000 adults per year is lower than estimates from the USA8,20,21 and Finland,4 similar to rates from England,3 and higher than previous Spanish estimates.6 We observed an increase in the incidence of pneumonia with age and a higher incidence among males than females,
Table 3
consistent with previous findings.4 The study period covered all seasons, and, as has been seen in most pneumonia studies, more cases occurred in the winter than in summer. A moderate influenza epidemic was observed in the winter during the study period, which may have temporarily increased the occurrence of pneumonia.22,23 We also observed a high incidence of pneumonia in the spring. This could be related to endemic infections in our geographical area, such as the presence of pneumonia by Q fever,24,25 although this was not evaluated in this study. As expected, the 30-day mortality increased with age, from 0.2% among those aged 18e64 years to 8.1% among those aged 65 years and older. The overall hospitalization rate we observed (42.8%) is consistent with the rate seen in Finland,4 lower than rate reported in other studies carried out in Spain,6 and higher than reported in the UK3 and the USA.7 These differences may reflect variations in practice from country to country and/or ease of access to hospital care. Of note, half of the patients whose CAP was managed on an outpatient basis were initially seen and diagnosed in the emergency department. As has been observed in previous studies,26,27 the management of CAP in the Comarca Interior region was characterized by proper clinical evaluation of the initial severity of the disease and appropriate identification of patients who could be treated on an ambulatory basis. As a result, 96.9% of such patients avoided subsequent hospitalization and there were no deaths in this group. Interestingly, the 97.4% of the patients treated by FPs as outpatients had mild pneumonia (CURB-65 score <2). Our study underscores the importance of assessing the severity of CAP and highlights the need for a close relationship between FPs and their patients to avoid unnecessary referrals or admission to the hospital. Quinolones predominated as the initial antibiotic choice for the treatment, prescribed for 58.5% of all patients and 49.1% of outpatients. This empirical strategy is consistent with SEPAR guidelines15 and with European recommendations when the national/local rate of bacterial resistance is clinically relevant,28 which may justify the higher rate of quinolone use observed in our study compared with the rate of use seen elsewhere.29,30 Greater dependence on quinolones as initial therapy suggests concern regarding
Outcomes of patients with community-acquired pneumonia in northern Spain.
Outcomes
All (N Z 960)
Inpatients (N Z 418)
Outpatients (N Z 542)
P value
In-hospital mortality Mortality within 30 days Admission to intensive care unit Use of mechanical ventilation Treatment failure Septic shock Severe sepsis
e 38 (4) 18 (1.9) 4 (0.4) 48 (5) 12 (1.3) 197 (20.8)
22 (5.3) 38 (9.1) 18 (4.3) 4 (1) 39 (9.3) 12 (2.9) 185 (45.7)
e 0 (0) 0 (0) 0 (0) 9 (1.7) 0 (0) 12 (2.2)
e <0.0001 <0.0001 0.036 <0.0001 <0.0001 <0.0001
Length of hospital staya (days) Mean (SD) >3 Return to daily activitya, mean (SD), days
e e 18.8 (10.8)
3.5 (2.5) 162 (38.8) 19.7 (9.2)
e e 18.2 (11.6)
0.0007
SD Z standard deviation; Data are presented as numbers (percentage) unless otherwise stated. Percentages exclude patients with missing data. Treatment failure, septic shock, and severe sepsis are defined in text. P value, between inpatients and outpatients. a Deaths are excluded.
370 the potential for the development of antibiotic resistance in the community. Among hospitalized patients, more than 80% were prescribed antibiotic strategies that closely followed national guidelines.15,16 In contrast, there was poor adherence to guidelines for antibiotic therapy for patients treated on an ambulatory basis, as has been seen in other studies.27 In our study, monotherapy with a b-lactam or macrolide was prescribed for almost 50% of ambulatory patients. This strategy is not consistent with SEPAR15 and IDSA/ATA guidelines.16 The initial choice of an antimicrobial agent is essential, since the likelihood of adverse outcomes increases with the use of inappropriate agents.31,32 That said, in our study the management of ambulatory patients was effective, as seen in other study,27 in spite of the frequent use of antibiotic strategies not endorsed by SEPAR guidelines.15 These recommendations are justified given the widespread prevalence of clinically relevant antibiotic resistance in the population, especially high pneumococcal macrolide resistance33 and the prevalence of atypical pathogens.34 However, data on bacterial resistance rates are from microbiological cultures, only a very small proportion of which originate from primary care. Thus, these rates are likely an overestimation of bacterial resistance in the community. An alternative explanation is that CAP can sometimes be a self-limiting infection. Anyway, current available evidence is insufficient to make recommendations for the choice of antibiotic to be used for treatment of CAP in ambulatory patients.35 This is a population study with the participation of 150 FPs. Fully participation of all FP is not assured and, therefore, we must assume as a limitation the fact that the real incidence of pneumonia was quite likely underestimate in our study since not all real cases would have been included. However, we made every effort to identify all patients with CAP in the catchment area. All primary health care centers were closely supervised by a local FP affiliated with the study, and all information was coordinated by a member of research team. In addition, we identified all patients evaluated in the emergency department of the area’s hospital for CAP. As a result, our study presents data that is representative of the total population of a defined geographic area, and consequently avoids selection bias. Patients with CAP diagnosed and treated by private physicians were not accessible for this study. While this could bias the results, the number of cases of CAP diagnosed by private physicians in our public health care system is in all likelihood quite small. Conclusions: although this study reflects the local practice in an area of northern Spain, it is an important addition to the literature regarding the incidence and management of CAP in the general community. Our study confirms that CAP imposes a heavy burden on health services, and provides current data on its management. Our incidence estimate of 3.1 cases/1000 adults per year is from an industrialized country with a temperate climate. Although the identification of patients for ambulatory treatment was satisfactory, choosing the appropriate antibiotic strategy for these patients is problematic, in part because the recommendations in national guidelines are not based on data from ambulatory patients. Our data corroborate the excellent outcomes of patients with mild pneumonia treated on an outpatient basis. Similar studies
A. Capelastegui et al. are needed to adequately gauge the incidence and management of CAP in other regions.
Conflict of interest None.
Acknowledgements We appreciate the support of the Direction of Comarca Interior and Galdakao Hospital, staff members of the different services, and family physicians of Comarca Interior. We also wish to thank Mr. Patrick J. Skerrett for his assistance editing the manuscript.
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22.
23. 24. 25.
Society of Pulmonology and Thoracic Surgery (SEPAR). Arch Bronconeumol 2005;41:272e89. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia. Clin Infect Dis 2007;44:S27e72. Levy MM, Fink M, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250e6. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143:29e36. Hanley JA, McNeil BJ. A method of comparing areas under receiver operating characteristic curves derived from the same cases. Radiology 1983;148:839e43. Foy HM, Kenny GE, Cooney MK, et al. Long-term epidemiology of infections with mycoplasma pneumoniae. J Infect Dis 1979; 139:681e7. Foy HM, Cooney MK, Allan I, et al. Rates of pneumonia during influenza epidemics in Seattle, 1964 to 1975. JAMA 1979; 241:253e8. Barker WH, Mullooly JP. Impact of epidemic type A influenza in a defined adult population. Am J Epidemiol 1980;112: 798e813. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev 1982;4:25e44. Sobradillo V, Zalacain R, Capelastegui A, et al. Antibiotic treatment in pneumonia due to Q fever. Thorax 1992;47:276e8. Sobradillo V, Ansola P, Baranda F, et al. Q fever pneumonia: a review of 164 community-acquired cases in the Basque country. Eur Respir J 1989;2:263e6.
371 26. Marrie TJ, Peeling RW, Fine MJ, et al. Ambulatory patients with community-acquired pneumonia: the frequency of atypical agents and clinical course. Am J Med 1996;101:508e15. 27. Fantin B, Aubert JP, Unger P, et al. Clinical evaluation of the management of community-acquired pneumonia by General Practitioners in France. Chest 2001;120:185e92. 28. Woodhead M, Blasi F, Ewig S, et al. Guidelines for the management of adult lower respiratory tract infections. Eur Respir J 2005;26:1138e80. 29. Malcolm C, Marrie TJ. Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting. Arch Intern Med 2003;163:797e802. 30. Arnold FW, Summersgill JT, Lajoie AS, et al. A Worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir Crit Care Med 2007;175:1086e93. 31. Menendez R, Torres A, Zalacain R, et al. Guidelines for the treatment of community-acquired pneumonia. Predictors of adherence and outcome. Am J Respir Crit Care Med 2005;172:757e62. 32. Mortensen EM, Restrepo M, Anzueto A, et al. Effects of guideline-concordant antimicrobial therapy on mortality among patients with community-acquired pneumonia. Am J Med 2004; 117:726e31. 33. Aspa J, Rajas O, Rodriguez de Castro F, et al. Drug-resistant pneumococcal pneumonia: clinical relevante and related factors. Clin Infect Dis 2004;38:787e98. 34. Zalacain R, Talayero N, Achotegui V, et al. Community acquired pneumonia. Reliability of the criteria for deciding ambulatory treatment. Arch Bronconeumol 1997;33:74e9. 35. Bjerre LM, Verheij TJ, Kochen MM. Antibiotics for community acquired pneumonia in adult outpatients. Cochrane Database Syst Rev 2004;2:CD002109.
www.elsevierhealth.com/journals/jinf
Study of community-acquired pneumonia: Incidence, patterns of care, and outcomes in primary and hospital care* ˜a a, Amaia Bilbao b, Julio Gamazo c, Alberto Capelastegui a,*, Pedro P. Espan ˜aki Gorostiaga d, Cristobal Esteban a, Federico Medel d, Juan Salgado d, In Lander Altube a, Inmaculada Gorordo a, Jose M. Quintana e, on behalf of Poblational Study of Pneumonia (PSoP) Group a
Pneumology Service Hospital Galdakao, 48960 Galdakao, Bizkaia, Spain Basque Foundation for Health Innovation and Research (BIOEF) e CIBERESP, Sondika, Bizkaia, Spain c Emergency Service Hospital Galdakao, Galdakao, Bizkaia, Spain d General Practice Comarca Interior, Bizkaia, Spain e Research Unit Hospital Galdakao e CIBERESP, Galdakao, Bizkaia, Spain b
Accepted 5 July 2010 Available online 6 August 2010
KEYWORDS Pneumonia; Epidemiology; Management
Summary Background: To asses the incidence, patterns of care, and outcomes of community-acquired pneumonia (CAP) in the population of a defined geographic area. Methods: Prospective study conducted from April 1, 2006, to June 30, 2007. All adult patients (age 18) with CAP in the Comarca Interior region of northern Spain were identified through the region’s 150 family physicians and the emergency department (ED) of the area’s general teaching hospital. Results: During a 15-month period, 960 patients with CAP were identified: 418 hospitalized and 542 ambulatory patients. The hospitalization rate was 43.5% and the global 30-day mortality was 4% (38 patients). Of the patients treated at home, most (90.4%) had mild pneumonia, only 3.1% (17 patients) were subsequently hospitalized, with a 30-day mortality rate of 0%. However, 48.9% were not treated according to antibiotic recommendations of the Spanish Society of Pneumology. Mean duration of return to daily activity was 18.8 days for the entire population. The incidence study was restricted to the first 12 months, during which 787 patients
Abbreviations: AUC, area under the receiver operating characteristic curve; CI, confidence interval; CAP, community-acquired pneumonia; CURB-65, confusion, urea nitrogen, respiratory rate, blood pressure, age 65 years; CRB-65, confusion, respiratory rate, blood pressure, age 65 years; FP, family physician; ICU, intensive care unit; IDSA/ATS, Infectious Diseases Society of America/American Thoracic Society; ROC, receiver operating characteristic curve; SEPAR, Spanish Society of Pneumology. * Sources of support: Basque Health Care Service. * Corresponding author. Tel./fax: þ34 944007002. E-mail address: [email protected] (A. Capelastegui). 0163-4453/$36 ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2010.07.015
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fulfilled the inclusion criteria. This represented an incidence of pneumonia of 3.1/1000 adults per year. Both the incidence of CAP and hospitalization for it rose with age. Conclusions: Our study offers information about CAP in the general population and provides feedback for the management of CAP. Although the selection of patients to be treated at home was appropriate, the choice of empiric antibiotic therapy for ambulatory CAP was problematic. ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Background Community-acquired pneumonia (CAP) is a major cause of morbidity in the community. It requires numerous family physician (FP) visits each year as well as a substantial number of hospital admissions,1,2 and thus imposes great burdens on health services. Most studies of CAP have been based on selected series of hospitalized patients. However, 40e80% of adults with CAP are treated on an ambulatory basis,3e7 and little information is available about this population. True incidence data are essential for the development of rational prevention programs, the allocation of health care resources, and the identification of changes in disease patterns. The incidence of CAP reported in developed countries has ranged from 1.6/1000 to 16/1000 per year.3,4,6,8 Of the few population-based incidence studies reported, the populations assessed have been small (<100,000 inhabitants), and all of the studies were conducted at least 10 years ago. A study conducted in Denmark showed that incidence of pneumonia requiring hospitalization has increased by 50% from 1994 to 2004, with a persistent high mortality rate.9 It is possible that the pattern of adult CAP may be changing elsewhere, particularly in patients not admitted to hospital, given the promotion of fluoroquinolones for the treatment of CAP and the implementation of clinical prediction rule. Updated knowledge about the management of inpatients and outpatients with CAP may raise questions regarding the current care of patients with CAP and offer new strategies for treatment. However, although there have been several reports on adults with CAP admitted to hospital,10e12 there have been no recent, comprehensive population-based studies including outpatients treated by FPs as well as hospitalized patients. The objective of our study was to provide a contemporary assessment of the incidence, patterns of care, and outcomes of CAP in the population of a defined geographic area. To do so, we conducted a study of all cases of CAP in a population aged 18 years or older of our area during a 15month period.
Country.13 Health care in this region is provided by the public network of the Basque Health Care Service-Osakidetza, which provides free unrestricted care to nearly 100% of the population. The study was conducted from April 1, 2006, to June 30, 2007. Patients were recruited from a teaching hospital (Galdakao Hospital), the only hospital in the area, and 150 FPs working in the Comarca Interior region. We instituted an extensive information campaign among all FPs serving the study population to make practitioners aware of the study and ask them to alert us to patients with CAP. By study protocol, patients with suspected pneumonia underwent x-ray. All adult cases of confirmed pneumonia that occurred during the study period were prospectively and consecutively enrolled in the incidence study. A member of the research team checked all discharge diagnoses of hospitalized patients and added previously unidentified cases who fulfilled the criteria to the study population. All eligible participant patients were informed of the study goals and gave informed consent to participate in the study. The project was approved by the hospital’s ethics review board.
Definition of pneumonia Community-acquired pneumonia was defined as pulmonary infiltrate on chest radiograph not known to be old and symptoms consistent with pneumonia, including cough, dyspnea, fever, and/or pleuritic chest pain not acquired in a hospital or a nursing home residence. Patients were excluded if they were known to be positive for human immunodeficiency virus, were chronically immunosuppressed (defined as immunosuppression for solid organ transplantation, postsplenectomy, receiving 10 mg/day of prednisone or the equivalent for more than 30 days, treatment with other immunosuppressive agents, or neutropenia, i.e., <1.0 109/L neutrophils), or who had been discharged from an acute care hospital or an on-site subacute care unit or from palliative care within the previous 14 days. Cases were confirmed if there was a radiological finding suggestive of pneumonic infiltrate as reviewed by two members of the research team (PPE and AC).
Patients and methods Patient management Setting and study population The Comarca Interior region, situated in the Basque Country (northern Spain), has a mixed urban, suburban, and rural population of 300,299 (254,523 aged 18). The age distribution, education level, sources of employment, socioeconomic status, and health care services of the urban population are representative of the overall Basque
Management for patients who initially visited an FP was left to the FP’s discretion. Patients presenting to the emergency department of GaldakaoHospital during the study period were managed according to a clinical guideline.12 As part of the clinical guideline, after patients were discharged they were managed by their own FP, with a follow-up visit to the hospital within 30 days of discharge.
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Measurements and management evaluation Clinical and demographic characteristics of each patient were recorded, along with all of the variables for the CURB-65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, age 65 years) score14 within the first 24 h after diagnosis. Process-of-care variables included the therapy employed (recorded as initial choice of antibiotic treatment, whether or not it was consistent with recommendations of the Spanish Society of Pneumology (SEPAR)15 or the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines,16 and antibiotics taken prior to admission), and the duration of antibiotic therapy. Outcome measures included vital status at 30 days after diagnosis; in-hospital mortality; admission to the intensive care unit (ICU); need for mechanical ventilation; septic shock (defined as systolic arterial tension <90 mmHg and requirement of vasopressors for a minimum of 4 h);
Table 1
treatment failure (defined as the development of clinical deterioration with hemodynamic instability, demonstrated respiratory failure or the appearance of it, required mechanical ventilation, demonstrated radiographic progression of pneumonia or the appearance of a new infectious foci, or had persistent fever or the reappearance of fever if change in treatment was needed); severe sepsis defined as sepsis associated with organ dysfunction and perfusion abnormalities17; hospital readmission within 30 days; length of hospital stay (calculated as the discharge date minus the admission date); length of time needed to return to normal daily activities; and subsequent hospitalization for patients initially treated as outpatients. Vital status and readmission information for all patients were initially determined by telephone interviews up to 90 days after discharge. All reported deaths and dates of death were confirmed by a review of medical reports, public death registries, or both.
Demographic and clinical characteristics of patients with community-acquired pneumonia in northern Spain.
Characteristics Host related Age, years, mean (SD) Range 18e44 45e64 65e74 >74 Women Immunized against influenza Immunized against pneumococcal infection Underlying diseases Neoplastic disease Liver disease Congestive heart failure Cerebrovascular disease Renal disease Chronic obstructive pulmonary disease Diabetes mellitus Number of comorbid conditions 0 1 >1 Severity of illness in admission CURB-65 scorea 0e1 2 >2 CRB-65 scoreb 0 1 >1 Bilateral or multilobe radiographic involvement
All (N Z 960)
Inpatients (N Z 418)
Outpatients (N Z 542)
P value
60 (20.3)
71.7 (16.6)
50.9 (18.1)
<0.0001 <0.0001
272 (28.3) 231 (24.1) 157 (16.4) 300 (31.3) 389 (40.5) 377 (41.8) 45 (5.1)
44 (10.5) 57 (13.6) 84 (20.1) 233 (55.7) 149 (35.7) 245 (63.3) 34 (9.3)
228 (42.1) 174 (32.1) 73 (13.5) 67 (12.4) 240 (44.3) 132 (25.6) 11 (2.1)
34 (3.5) 12 (1.3) 29 (3) 38 (4) 30 (3.1) 115 (12.3) 101 (10.8)
25 (6) 7 (1.7) 23 (5.5) 33 (7.9) 22 (5.3) 83 (20.5) 71 (17.6)
9 (1.7) 5 (0.9) 6 (1.1) 5 (0.9) 8 (1.5) 32 (6) 30 (5.6)
660 (71) 198 (21.3) 71 (7.6)
214 (53.1) 132 (32.8) 57 (14.1)
446 (84.8) 66 (12.6) 14 (2.7)
670 (69.8) 193 (20.1) 97 (10.1)
180 (43.1) 145 (34.7) 93 (22.3)
490 (90.4) 48 (8.9) 4 (0.7)
449 383 128 111
71 (17) 230 (55) 117 (28) 99 (24.6)
378 (69.7) 153 (28.2) 11 (2) 12 (2.3)
0.007 <0.0001 <0.0001 0.0003 0.298 <0.0001 <0.0001 0.0008 <0.0001 <0.0001 <0.0001
<0.0001
<0.0001 (46.8) (39.9) (13.3) (12)
<0.0001
SD, standard deviation; Data are presented as numbers (percentage) unless otherwise stated. Percentages exclude patients with missing data. P value, between inpatients and outpatients. a Severity of illness on admission assessed with CURB-65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, age 65 years) score. b Severity of illness on admission assessed with CRB-65 (Confusion, Respiratory rate, Blood pressure, age 65 year) score.
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Chi-square and Fisher’s exact tests were performed for the comparison of categorical variables, and the Student t test and non-parametric Wilcoxon test were performed for continuous variables. The incidence analysis was restricted to a 12-month period (April 1, 2006 to April 1, 2007). The predictive accuracy of the CURB-65 and CRB-65 (the same as the CURB-65 but without the urea measurement) severity scores was determined by calculating the area under the receiver operating characteristic (ROC) curve.18 Area under the curve (AUC) values was compared using the non-parametric method described by Hanley and NcNeil.19 All effects were considered significant at P < 0.05. All statistical analyses were performed using SAS for Windows statistical software, version 9.2 (SAS Institute, Inc., Carey, NC).
Results
12
12
250
10
10
200
8
150
6
100
4
8 6 4
50
2
2
0
0
0
18-44
45-64
65-74
>74
Incidence of hospitalization (per 1 ,000 pop)
300
Incidence (per 1, 000 pop)
Number of cases
During a 15-month period, 960 patients with CAP fulfilled the inclusion criteria. Of these, 542 were initially treated on an outpatient basis and 418 were initially hospitalized for treatment. Only 13 (1.4%) of the patients were identified retrospectively from the hospital database; their demographic variables, coexisting conditions, and severity of CAP upon admission were similar to those of the hospitalized patients recruited prospectively. Characteristics of the entire study cohort are provided in Table 1. Compared with hospitalized patients, those treated on an outpatient basis were significantly younger, more likely to be female, had fewer comorbidities, and had a lower severity of CAP. Among the 542 patients managed on an outpatient basis, 269 (49.6%) were initially attended to and diagnosed by an FP, while 273 were initially attended to and diagnosed in the emergency department of Galdakao Hospital. Demographic variables, coexisting conditions, CAP severity upon admission, and outcomes were similar
Age (years)
for these two group with the exception of the prescription of antibioticsdpatients initially seen by an FP had the lowest use of quinolones and higher use of macrolides (p < 0.0001).
Community incidence of CAP A total of 787 patients who fulfilled the inclusion criteria from April 1, 2006 to April 1, 2007 were included in the incidence study. This represented an incidence of CAP of 3.1/1000 adults per year. The age-specific number of cases and incidence are shown in Fig. 1. The incidence rose more than five-fold with age from 1.7 per 1000 in those aged 18e44 years to 9.9 per 1000 in those aged 74 years and older. The incidence of hospitalized CAP in those 65 years or older was 4.9 cases per 1000 population. Pneumonia incidence rates were lower during the summer than during the winter and spring (p < 0.0001) (Fig. 2).
Management and outcomes We assessed the severity of illness at diagnosis using the CURB-65 and CRB-65 scores. A CURB-65 score 2 was 94.7% sensitive and 72.5% specific at predicting 30-day mortality (negative predictive value (NPV), 99.7%; positive predictive value (PPV), 12.4%), while a CRB-65 score 1 was 97.4% sensitive and 48.6% specific (NPV, 99.8%; PPV, 7.2%). The CURB-65 and CRB-65 scores performed equally well with regard to the prediction of 30-day mortality (AUC 0.90 versus 0.87, p Z 0.0501, Fig. 3). Antibiotics initially prescribed for CAP patients are shown in Table 2. Statistically significant differences were observed among inpatients and outpatients. Prescriptions for the treatment of CAP were, in rank order, a quinolone (58.5%), b-lactams (24%), macrolides (10.6%), and b-lactams/macrolides (5.8%). Almost half (48.9%) of ambulatory patients were not treated according to antibiotic recommendations of SEPAR. 140 120 100
No.of patients
Statistical analysis
18-44 years
80
45-64 years 65-74 years
60
>74 years
40 20 0
A 2006
Figure 1 Age-specific number of cases, incidence rate per 1000 inhabitants, and rate of hospitalization per 1000 inhabitants in patients with community-acquired pneumonia in northern Spain. Incidence of pneumonia (diamonds) and incidence of hospitalization (rectangles) rose with age across all age group (p < 0.0001). Bars Z Number of cases by age categories.
M
J
J
A
S
O
Months
N
D
J
F
M
2007
Figure 2 Age-specific number of cases of communityacquired pneumonia by month of diagnosis in patients with community-acquired pneumonia in northern Spain. Incidence rate per 1,000 inhabitants over the course of the year was 1.2 in winter, 0.8 in spring, 0.6 in summer, and 0.6 in autumn (p<0.0001).
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9.1% (38 cases) compared with 0% among those treated on an ambulatory basis. Morbidity was also low among ambulatory patients, with 17 (3.1%) requiring hospitalization d9 due to treatment failure, 3 for pleural effusion, 2 for respiratory insufficiency, 1 for a myocardial infarction, 1 for lung cancer, 1 for urticariad but with no deaths or ICU admissions. Mean duration of return to daily activity in the entire population was 18.8 days, with outpatients returning to daily activity 1.5 days sooner than inpatients (p Z 0.0007). For the 324 patients who were employed at the time of their CAP diagnosis, the period of sick leave was recorded for 274 (84.6%). Of these, 17 (6.2%) returned to work within one week, 34 (12.4%) within two weeks, and 242 (88.3%) within one month, while 32 (11.7%) were absent for longer than one month. The mean time away from work for all employed patients was 25.5 days, with outpatients returning 3.3 days sooner than inpatients (p Z 0.0004).
S e n s i t i vi t y
,75
,50
,25 ______ CURB65 (AUC = 0.90, 95%CI = 0.85 to 0.95) ____
0,00 0,00
,25
CRB65 (AUC = 0.87, 95%CI = 0.82 to 0.93)
,50
,75
1,00
Discussion
1 - Specificity
Figure 3 Receiver-operator-characteristic curves of predicting 30-day mortality according to CURB-65 and CRB-65 scores. AUCZarea under the curve; CIZconfidence interval. The CURB-65 and CRB-65 scores performed equally well with regard to the prediction of 30-day mortality (pZ0.0501).
The hospitalization rate was 43.5%. Among patients initially seen and diagnosed by an FP (269 cases), 97.4% were treated at home, compared to 39.5% (273 cases) of patients initially seen and diagnosed in the emergency department of Galdakao Hospital. The age-specific rates in admission, mortality, and hospitalization are shown in Fig. 4. Outcomes among inpatients and outpatients are shown in Table 3. The mortality rate among hospitalized patients was
Table 2
In this prospective study, we assessed the incidence, patterns of care, and clinical outcomes of CAP in the entire adult population of the Comarca Interior region of northern Spain. We confirmed the substantial burden of CAP, estimating an annual incidence of 3.1 cases per 1000 adults per year, a 42.8% rate of hospital admission, and a CAPinduced period of inactivity of almost 20 days. We observed that the management of hospitalized and ambulatory patients was generally effective, although the prescription of antibiotics for outpatients was often not in agreement with the recommendations of established guidelines. We also observed that patients selected for ambulatory treatment were appropriately identified, with 90.4% having mild pneumonia and CURB-65 scores generally <2. Both the CURB-65 and CRB-65 scores were good predictors of 30-day mortality (AUC 0.90 and AUC 0.87, respectively).
Process-of-care of patients with community-acquired pneumonia in northern Spain.
Process of care Antibiotics prescribed B-lactam Macrolide B-lactam/macrolide Fluoroquinolone Others Taking antibiotics prior to diagnosis Appropriate antibiotic therapy according Spanish guidelinesa Appropriate antibiotic therapy according American guidelinesa Antibiotics within 8 h Duration of antibiotic therapy after diagnosis, mean (SD), daysb Duration of intravenous therapy after diagnosis, mean (SD), daysb
All (N Z 960)
Inpatients (N Z 418)
Outpatients (N Z 542)
228 (24) 101 (10.6) 55 (5.8) 556 (58.5) 11 (1.2) 156 (17.3) 624 (65.6)
61 (14.6) 3 (0.7) 50 (12) 294 (70.5) 9 (2.2) 77 (20.3) 351 (84.2)
167 (31.3) 98 (18.4) 5 (0.9) 262 (49.1) 2 (0.4) 79 (15.1) 273 (51.1)
0.042 <0.0001
714 (75.1)
351 (84.2)
363 (68)
<0.0001
e 9.9 (2)
366 (89.3) 9.8 (2.2)
e 10 (1.8)
e 0.002
e
2.7 (2.4)
e
e
P value <0.0001
SD Z standard deviation; Data are presented as numbers (percentage) unless otherwise stated. Percentages exclude patients with missing data. P value, between inpatients and outpatients. a Appropriate antibiotic according Spanish guidelines (ref. 15). Appropriate antibiotic according U.S. guidelines (ref. 16). b In-hospital deaths are excluded.
A study of community-acquired pneumonia CURB65: 0-1
CURB65: 2
369
CURB65: >2
90
300
12
80
50
150
40 30
100
20
50
10 0
18-44
45-64
65-74
8 6 4
30 days mortality (%)
60
200
0
10
70 Hospitalization (%)
Number of cases
250
2 0
>74
Age (years)
Figure 4 Age-specific severity in admission, hospitalization and 30-day mortality in patients with community-acquired pneumonia in northern Spain. Hospitalization (diamonds) and mortality (rectangles) increased across all age groups (p < 0.0001). Bars Z number of cases according severity in admission measure by CURB-65 score.
Three truly community-based studies of pneumonia incidence were conducted in smaller populations in Finland (38,128 inhabitants aged 15),4 in Barcelona, Spain (74,368 inhabitants aged 14)6 and in Nottingham, England (53,137 inhabitants aged 15e79).3 The overall incidence of CAP was approximately 9/1000 in Finland, 1.6/1000 in Barcelona, and 4.7/1000 in Nottingham. In the United States, data from the National Health Interview Survey estimated the annual incidence of pneumonia for persons 18 years and older, including those treated in outpatient settings, at 16.3/1000 per year.8 Our study was based on a population of almost 300,000 adults, which is much larger than previous population-based studies. Our estimated annual incidence of 3.1/1000 adults per year is lower than estimates from the USA8,20,21 and Finland,4 similar to rates from England,3 and higher than previous Spanish estimates.6 We observed an increase in the incidence of pneumonia with age and a higher incidence among males than females,
Table 3
consistent with previous findings.4 The study period covered all seasons, and, as has been seen in most pneumonia studies, more cases occurred in the winter than in summer. A moderate influenza epidemic was observed in the winter during the study period, which may have temporarily increased the occurrence of pneumonia.22,23 We also observed a high incidence of pneumonia in the spring. This could be related to endemic infections in our geographical area, such as the presence of pneumonia by Q fever,24,25 although this was not evaluated in this study. As expected, the 30-day mortality increased with age, from 0.2% among those aged 18e64 years to 8.1% among those aged 65 years and older. The overall hospitalization rate we observed (42.8%) is consistent with the rate seen in Finland,4 lower than rate reported in other studies carried out in Spain,6 and higher than reported in the UK3 and the USA.7 These differences may reflect variations in practice from country to country and/or ease of access to hospital care. Of note, half of the patients whose CAP was managed on an outpatient basis were initially seen and diagnosed in the emergency department. As has been observed in previous studies,26,27 the management of CAP in the Comarca Interior region was characterized by proper clinical evaluation of the initial severity of the disease and appropriate identification of patients who could be treated on an ambulatory basis. As a result, 96.9% of such patients avoided subsequent hospitalization and there were no deaths in this group. Interestingly, the 97.4% of the patients treated by FPs as outpatients had mild pneumonia (CURB-65 score <2). Our study underscores the importance of assessing the severity of CAP and highlights the need for a close relationship between FPs and their patients to avoid unnecessary referrals or admission to the hospital. Quinolones predominated as the initial antibiotic choice for the treatment, prescribed for 58.5% of all patients and 49.1% of outpatients. This empirical strategy is consistent with SEPAR guidelines15 and with European recommendations when the national/local rate of bacterial resistance is clinically relevant,28 which may justify the higher rate of quinolone use observed in our study compared with the rate of use seen elsewhere.29,30 Greater dependence on quinolones as initial therapy suggests concern regarding
Outcomes of patients with community-acquired pneumonia in northern Spain.
Outcomes
All (N Z 960)
Inpatients (N Z 418)
Outpatients (N Z 542)
P value
In-hospital mortality Mortality within 30 days Admission to intensive care unit Use of mechanical ventilation Treatment failure Septic shock Severe sepsis
e 38 (4) 18 (1.9) 4 (0.4) 48 (5) 12 (1.3) 197 (20.8)
22 (5.3) 38 (9.1) 18 (4.3) 4 (1) 39 (9.3) 12 (2.9) 185 (45.7)
e 0 (0) 0 (0) 0 (0) 9 (1.7) 0 (0) 12 (2.2)
e <0.0001 <0.0001 0.036 <0.0001 <0.0001 <0.0001
Length of hospital staya (days) Mean (SD) >3 Return to daily activitya, mean (SD), days
e e 18.8 (10.8)
3.5 (2.5) 162 (38.8) 19.7 (9.2)
e e 18.2 (11.6)
0.0007
SD Z standard deviation; Data are presented as numbers (percentage) unless otherwise stated. Percentages exclude patients with missing data. Treatment failure, septic shock, and severe sepsis are defined in text. P value, between inpatients and outpatients. a Deaths are excluded.
370 the potential for the development of antibiotic resistance in the community. Among hospitalized patients, more than 80% were prescribed antibiotic strategies that closely followed national guidelines.15,16 In contrast, there was poor adherence to guidelines for antibiotic therapy for patients treated on an ambulatory basis, as has been seen in other studies.27 In our study, monotherapy with a b-lactam or macrolide was prescribed for almost 50% of ambulatory patients. This strategy is not consistent with SEPAR15 and IDSA/ATA guidelines.16 The initial choice of an antimicrobial agent is essential, since the likelihood of adverse outcomes increases with the use of inappropriate agents.31,32 That said, in our study the management of ambulatory patients was effective, as seen in other study,27 in spite of the frequent use of antibiotic strategies not endorsed by SEPAR guidelines.15 These recommendations are justified given the widespread prevalence of clinically relevant antibiotic resistance in the population, especially high pneumococcal macrolide resistance33 and the prevalence of atypical pathogens.34 However, data on bacterial resistance rates are from microbiological cultures, only a very small proportion of which originate from primary care. Thus, these rates are likely an overestimation of bacterial resistance in the community. An alternative explanation is that CAP can sometimes be a self-limiting infection. Anyway, current available evidence is insufficient to make recommendations for the choice of antibiotic to be used for treatment of CAP in ambulatory patients.35 This is a population study with the participation of 150 FPs. Fully participation of all FP is not assured and, therefore, we must assume as a limitation the fact that the real incidence of pneumonia was quite likely underestimate in our study since not all real cases would have been included. However, we made every effort to identify all patients with CAP in the catchment area. All primary health care centers were closely supervised by a local FP affiliated with the study, and all information was coordinated by a member of research team. In addition, we identified all patients evaluated in the emergency department of the area’s hospital for CAP. As a result, our study presents data that is representative of the total population of a defined geographic area, and consequently avoids selection bias. Patients with CAP diagnosed and treated by private physicians were not accessible for this study. While this could bias the results, the number of cases of CAP diagnosed by private physicians in our public health care system is in all likelihood quite small. Conclusions: although this study reflects the local practice in an area of northern Spain, it is an important addition to the literature regarding the incidence and management of CAP in the general community. Our study confirms that CAP imposes a heavy burden on health services, and provides current data on its management. Our incidence estimate of 3.1 cases/1000 adults per year is from an industrialized country with a temperate climate. Although the identification of patients for ambulatory treatment was satisfactory, choosing the appropriate antibiotic strategy for these patients is problematic, in part because the recommendations in national guidelines are not based on data from ambulatory patients. Our data corroborate the excellent outcomes of patients with mild pneumonia treated on an outpatient basis. Similar studies
A. Capelastegui et al. are needed to adequately gauge the incidence and management of CAP in other regions.
Conflict of interest None.
Acknowledgements We appreciate the support of the Direction of Comarca Interior and Galdakao Hospital, staff members of the different services, and family physicians of Comarca Interior. We also wish to thank Mr. Patrick J. Skerrett for his assistance editing the manuscript.
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