Rafael Zalacain

Risk factors of treatment failure in community acquired pneumonia: implications for disease outcome

Background: An inadequate response to initial empirical treatment of community acquired pneumonia (CAP) represents a challenge for clinicians and requires early identification and intervention. A study was undertaken to quantify the incidence of failure of empirical treatment in CAP, to identify risk factors for treatment failure, and to determine the implications of treatment failure on the outcome. Methods: A prospective multicentre cohort study was performed in 1424 hospitalised patients from 15 hospitals. Early treatment failure (<72 hours), late treatment failure, and in-hospital mortality were recorded. Results: Treatment failure occurred in 215 patients (15.1%): 134 early failure (62.3%) and 81 late failure (37.7%). The causes were infectious in 86 patients (40%), non-infectious in 34 (15.8%), and undetermined in 95. The independent risk factors associated with treatment failure in a stepwise logistic regression analysis were liver disease, pneumonia risk class, leucopenia, multilobar CAP, pleural effusion, and radiological signs of cavitation. Independent factors associated with a lower risk of treatment failure were influenza vaccination, initial treatment with fluoroquinolones, and chronic obstructive pulmonary disease (COPD). Mortality was significantly higher in patients with treatment failure (25% v 2%). Failure of empirical treatment increased the mortality of CAP 11-fold after adjustment for risk class. Conclusions: Although these findings need to be confirmed by randomised studies, they suggest possible interventions to decrease mortality due to CAP.

Drug-Resistant Pneumococcal Pneumonia: Clinical Relevance and Related Factors

A multicenter study of 638 cases of community-acquired pneumonia due to Streptococcus pneumoniae (SP-CAP) was performed to assess current levels of resistance. Of the pneumococcal strains, 35.7% had an minimum inhibitory concentration (MIC) of penicillin of > or =0.12 microg/mL (3 isolates had an MIC of 4 microg/mL), 23.8% had an MIC of erythromycin of 128 microg/mL, and 22.2% were multidrug resistant. Logistic regression determined that chronic pulmonary disease (odds ratio [OR], 1.44], human immunodeficiency virus infection (OR, 1.98), clinically suspected aspiration (OR, 2.12), and previous hospital admission (OR, 1.69) were related to decreased susceptibility to penicillin, and previous admission (OR, 1.89) and an MIC of penicillin of MIC > or =0.12 microg/mL (OR, 15.85) were related to erythromycin resistance (MIC, > or =1 microg/mL). The overall mortality rate was 14.4%. Disseminated intravascular coagulation, empyema, and bacteremia were significantly more frequent among patients with penicillin-susceptible SP-CAP. Among isolates with MICs of penicillin of > or =0.12 microg/mL, serotype 19 was predominant and was associated with a higher mortality rate. In summary, the rate of resistance to beta -lactams and macrolides among S. pneumoniae that cause CAP remains high, but such resistance does not result in increased morbidity.

Reaching Stability in Community-Acquired Pneumonia: The Effects of the Severity of Disease, Treatment, and the Characteristics of Patients

BACKGROUND The natural history of the resolution of infectious parameters in patients with community-acquired pneumonia (CAP) is not completely known. The aim of our study was to identify those factors related to host characteristics, the severity of pneumonia, and treatment that influence clinical stability. METHODS In a prospective, multicenter, observational study, we observed 1424 patients with CAP who were admitted to 15 Spanish hospitals. The main outcome variable was the number of days needed to reach clinical stability (defined as a temperature of <or=37.2 degrees C, a heart rate of <or=100 beats/min, a respiratory rate of <or=24 breaths/min, systolic blood pressure of >or=90 mm Hg, and oxygen saturation >or=90% or arterial oxygen partial pressure of >or=60 mm Hg). RESULTS The median time to stability was 4 days. A Cox proportional hazard model identified 6 independent variables recorded during the first 24 h after hospital admission related to the time needed to reach stability: dyspnea (hazard ratio [HR], 0.76), confusion (HR, 0.66), pleural effusion (HR, 0.67), multilobed CAP (HR, 0.72), high pneumonia severity index (HR, 0.73), and adherence to the Spanish guidelines for treatment of CAP (HR, 1.22). A second Cox model was performed that included complications and response to treatment. This model identified the following 10 independent variables: chronic bronchitis (HR, 0.81), dyspnea (HR, 0.79), confusion (HR, 0.61), multilobed CAP (HR, 0.84), initial severity of disease (HR, 0.73), treatment failure (HR, 0.31), cardiac complications (HR, 0.66), respiratory complications (HR, 0.77), empyema (HR, 0.57), and admission to the intensive care unit (HR, 0.57). CONCLUSIONS Some characteristics of CAP are useful at the time of hospital admission to identify patients who will need a longer hospital stay to reach clinical stability. Empirical treatment that follows guidelines is associated with earlier clinical stability. Complications and treatment failure delay clinical stability.

Community-acquired pneumonia in the elderly: Spanish multicentre study

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 (≥65 yrs) admitted to hospital for CAP. The study included 503 patients (age 76±7 yrs). The clinical picture lasted ≤5 days in 318 (63%) and the main clinical features were cough (n=407, 81%) and fever (n=380, 76%). Aetiological diagnosis was achieved in 199 (40%) cases, with a definite diagnosis obtained in 164 (33%). Of the 223 microorganisms isolated the main agents found were Streptococcus pneumoniae in 98 (49%) and Haemophilus influenzae in 27 (14%). A total of 53 patients died (11%) and the multivariate analysis showed the following factors of bad prognosis: previous bed confinement, alteration in mental status, absence of chills, plasma creatinine ≥1.4 mg·dL−1, oxygen tension in arterial blood/inspiratory oxygen fraction ratio <200 at the time of admission, and shock and renal failure during the evolution. 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.

Prospective Comparison of Severity Scores for Predicting Clinically Relevant Outcomes for Patients Hospitalized With Community-Acquired Pneumonia

BACKGROUND The comparative accuracy and discriminatory power of three validated rules for predicting clinically relevant outcomes other than mortality in patients hospitalized with community-acquired pneumonia (CAP) are unknown. METHODS We prospectively compared the newly developed severe community-acquired pneumonia (SCAP) score, pneumonia severity index (PSI), and the British Thoracic Society confusion, urea > 7 mmol/L, respiratory rate > or = 30 breaths/min, BP < 90 mm Hg systolic or < 60 mm Hg diastolic, age > or = 65 years (CURB-65) rule in an internal validation cohort of 1,189 consecutive adult inpatients with CAP from one hospital and an external validation cohort of 671 consecutive adult inpatients from three other hospitals. Major adverse outcomes were admission to ICU, need for mechanical ventilation, progression to severe sepsis, or treatment failure. Mean hospital length of stay (LOS) was also evaluated. The rules were compared based on sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic. RESULTS The rate of all adverse outcomes and hospital LOS increased directly with increasing SCAP, PSI, or CURB-65 scores (p < 0.001) in both cohorts. Patients classified as high risk by the SCAP score showed higher rates of adverse outcomes (ICU admission, 35.8%; mechanical ventilation, 16.4%; severe sepsis, 98.5%; treatment failure, 22.4%) than PSI and CURB-65 high-risk classes. The discriminatory power of SCAP, as measured by AUC, was 0.75 for ICU admission, 0.76 for mechanical ventilation, 0.79 for severe sepsis, and 0.61 for treatment failure in the external validation cohort. AUC differences with PSI or CURB-65 were found. CONCLUSIONS The SCAP score is as accurate or better than other current scoring systems in predicting adverse outcomes in patients hospitalized with CAP while helping classify patients into different categories of increasing risk for potentially closer monitoring.

Microbial aetiology of healthcare associated pneumonia in Spain: a prospective, multicentre, case-control study.

Introduction Healthcare-associated pneumonia (HCAP) is actually considered a subgroup of hospital-acquired pneumonia due to the reported high risk of multidrug-resistant pathogens in the USA. Therefore, current American Thoracic Society/Infectious Diseases Society of America guidelines suggest a nosocomial antibiotic treatment for HCAP. Unfortunately, the scientific evidence supporting this is contradictory. Methods We conducted a prospective multicentre case–control study in Spain, comparing clinical presentation, outcomes and microbial aetiology of HCAP and community-acquired pneumonia (CAP) patients matched by age (±10 years), gender and period of admission (±10 weeks). Results 476 patients (238 cases, 238 controls) were recruited for 2 years from June 2008. HCAP cases showed significantly more comorbidities (including dysphagia), higher frequency of previous antibiotic use in the preceding month, higher pneumonia severity score and worse clinical status (Charslon and Barthel scores). While microbial aetiology did not differ between the two groups (HCAP and CAP: Streptococcus pneumoniae: 51% vs 55%; viruses: 22% vs 12%; Legionella: 4% vs 9%; Gram-negative bacilli: 5% vs 4%; Pseudomonas aeruginosa: 4% vs 1%), HCAP patients showed worse mortality rates (1-month: HCAP, 12%; CAP 5%; 1-year: HCAP, 24%; CAP, 9%), length of hospital stay (9 vs 7 days), 1-month treatment failure (5.5% vs 1.5%) and readmission rate (18% vs 11%) (p<0.05, each). Conclusions Despite a similar clinical presentation, HCAP was more severe due to patients’ conditions (comorbidities) and showed worse clinical outcomes. Microbial aetiology of HCAP did not differ from CAP indicating that it is not related to increased mortality and in Spain most HCAP patients do not need nosocomial antibiotic coverage.

Initial management of pneumonia and sepsis: factors associated with improved outcome.

Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

Tobacco Smoking Increases the Risk for Death From Pneumococcal Pneumonia

BACKGROUND Active smoking increases the risk of developing community-acquired pneumonia (CAP) and invasive pneumococcal disease, although its impact on mortality in pneumococcal CAP outcomes remains unclear. The aim of this study was to investigate the influence of current smoking status on pneumococcal CAP mortality. METHODS We performed a multicenter, prospective, observational cohort study in 4,288 hospitalized patients with CAP. The study group consisted of 892 patients with pneumococcal CAP: 204 current smokers (22.8%), 387 nonsmokers (43.4%), and 301 exsmokers (33.7%). RESULTS Mortality at 30 days was 3.9%: 4.9% in current smokers vs 4.3% in nonsmokers and 2.6% in exsmokers. Current smokers with CAP were younger (51 years vs 74 years), with more alcohol abuse and fewer cardiac, renal, and asthma diseases. Current smokers had lower CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) scores, although 40% had severe sepsis at diagnosis. Current smoking was an independent risk factor (OR, 5.0; 95% CI, 1.8-13.5; P = .001) for 30-day mortality of pneumococcal CAP after adjusting for age (OR, 1.06; P = .001), liver disease (OR, 4.5), sepsis (OR, 2.3), antibiotic adherence to guidelines, and first antibiotic dose given < 6 h. The independent risk effect of current smokers remained when compared only with nonsmokers (OR, 4.0; 95% CI, 1.3-12.6; P = .015) or to exsmokers (OR, 3.9; 95% CI, 1.09-4.95; P = .02). CONCLUSIONS Current smokers with pneumococcal CAP often develop severe sepsis and require hospitalization at a younger age, despite fewer comorbid conditions. Smoking increases the risk of 30-day mortality independently of tobacco-related comorbidity, age, and comorbid conditions. Current smokers should be actively targeted for preventive strategies.

Validation and comparison of SCAP as a predictive score for identifying low-risk patients in community-acquired pneumonia.

PURPOSES (1) To validate the Severe Community Acquired Pneumonia (SCAP) score in predicting 30-day mortality. (2) To validate its ability to identifying patients at low risk of death. (3) To compare it against the Pneumonia Severity Index (PSI), and the British Thoracic Societys CURB-65 rules. METHODS The SCAP score was validated to predict 30-day mortality in an internal validation cohort of consecutive adult patients seen in one hospital. Consecutive inpatients from other three hospitals were used to externally validate the score and compare the SCAP with the PSI and CURB-65. The discriminatory power of these rules to predict 30-day mortality was tested by the Area under Curve (AUC), and their predictive accuracy with the sensitivity, specificity and predictive values. RESULTS The 30-day mortality rate increased directly with increasing SCAP score (class 0: 0.5%, to class 4: 66.5% risk) in the internal validation cohort, and from 1.3% to 29.2% in external cohort (P<0.001) with an AUC of 0.83 and 0.75, respectively (P=0.024). The SCAP score identified 62.4% (95% IC 58.8-66.0) low-risk patients, 52.5% (95% IC 48.8-56.2) the PSI and 46.2% (95% CI 42.5-49.9) the CURB-65 in the external cohort. Patients classified as low risk by the three rules had similar 30-day mortality (SCAP: 2.5%, PSI: 1.6% and CURB-65: 2.7%). CONCLUSION The SCAP is valid to predict 30-day mortality among low-risk patients and identifies a larger proportion of patients as low-risk than the other studied rules.

Development of a prognostic index for 90-day mortality in patients discharged after admission to hospital for community-acquired pneumonia

Background: Although patients admitted to hospital for community-acquired pneumonia (CAP) experience substantial short-term mortality following hospital discharge, few studies have focused on identifying factors that predict mortality after admission to hospital in this population. The objective of this study was to develop and validate a prognostic index for 90-day mortality after hospital discharge among patients with CAP. Methods: The prognostic index was derived in 1117 adult patients discharged between 2003 and 2007 from a general hospital following admission for CAP. It was validated in 646 consecutive patients with CAP discharged from three other hospitals between 1 November 2005 and 31 July 2006. Risk factors evaluated included host-related factors, severity upon admission, in-hospital management and bacteriology. Results: In the derivation cohort, three factors were independently associated with 90-day mortality: pre-illness functional status, Charlson index (composite measure of co-morbid illnesses) and severity on admission. Mortality at 90 days was 0.7% in the low-risk group, 3.5% in the intermediate-risk group and 17.2% in the high-risk group. In the validation cohort, 90-day mortality in the three groups was 0.6%, 3.9% and 19.6%, respectively. Compared with the low-risk group, the odds ratio for mortality was 43.5 for the high-risk group. The risk categories showed an area under the receiver operating characteristic curve of 0.79 in the derivation cohort and 0.82 in the validation cohort. Conclusions: The prognostic index accurately stratifies patients admitted to hospital for CAP into low-, intermediate- and high-risk groups for 90-day mortality on discharge. The use of this index could help clinicians improve outcomes in this vulnerable population by targeting specific interventions to each group.