BACKGROUND: The choice of empirical antibiotic treatment for patients with clinically suspected community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. We compared strategies of empirical treatment (allowing deviations for medical reasons) with beta-lactam monotherapy, beta-lactam-macrolide combination therapy, or fluoroquinolone monotherapy.
METHODS: In a cluster-randomized, crossover trial with strategies rotated in 4-month periods, we tested the noninferiority of the beta-lactam strategy to the beta-lactam-macrolide and fluoroquinolone strategies with respect to 90-day mortality, in an intention-to-treat analysis, using a noninferiority margin of 3 percentage points and a two-sided 90% confidence interval.
RESULTS: A total of 656 patients were included during the beta-lactam strategy periods, 739 during the beta-lactam-macrolide strategy periods, and 888 during the fluoroquinolone strategy periods, with rates of adherence to the strategy of 93.0%, 88.0%, and 92.7%, respectively. The median age of the patients was 70 years. The crude 90-day mortality was 9.0% (59 patients), 11.1% (82 patients), and 8.8% (78 patients), respectively, during these strategy periods. In the intention-to-treat analysis, the risk of death was higher by 1.9 percentage points (90% confidence interval [CI], -0.6 to 4.4) with the beta-lactam-macrolide strategy than with the beta-lactam strategy and lower by 0.6 percentage points (90% CI, -2.8 to 1.9) with the fluoroquinolone strategy than with the beta-lactam strategy. These results indicated noninferiority of the beta-lactam strategy. The median length of hospital stay was 6 days for all strategies, and the median time to starting oral treatment was 3 days (interquartile range, 0 to 4) with the fluoroquinolone strategy and 4 days (interquartile range, 3 to 5) with the other strategies.
CONCLUSIONS: Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality. (Funded by the Netherlands Organization for Health Research and Development; CAP-START ClinicalTrials.gov number, NCT01660204.).
IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90mmHg, temperature <38.0° C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7. RESULTS After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6%difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95%CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95%CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95%CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95%CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9%vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. Copyright 2014 American Medical Association. All rights reserved.
IMPORTANCE: Nearly every US acute care hospital reports publicly on adherence to recommended processes of care for patients hospitalized with pneumonia. However, it remains uncertain how much performance of these process measures has improved over time or whether performance is associated with superior patient outcomes.
OBJECTIVES: To describe trends in processes of care, mortality, and readmission for elderly patients hospitalized for pneumonia and to assess the independent associations between processes and outcomes of care.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study conducted from January 1, 2006, to December 31, 2010, at 4740 US acute care hospitals. The cohort included 1 818 979 cases of pneumonia in elderly (≥65 years), Medicare fee-for-service patients who were eligible for at least 1 of 7 pneumonia inpatient processes of care tracked by the Centers for Medicare & Medicaid Services (CMS).
MAIN OUTCOMES AND MEASURES: Annual performance rates for 7 pneumonia processes of care and an all-or-none composite of these measures; and 30-day, all-cause mortality and hospital readmission, adjusted for patient and hospital characteristics.
RESULTS: Adjusted annual performance rates for all 7 CMS processes of care (expressed in percentage points per year) increased significantly from 2006 to 2010, ranging from 1.02 for antibiotic initiation within 6 hours to 5.30 for influenza vaccination (P < .001). All 7 measures were performed in more than 92% of eligible cases in 2010. The all-or-none composite demonstrated the largest adjusted relative increase over time (6.87 percentage points per year; P < .001) and was achieved in 87.4% of cases in 2010. Adjusted annual mortality decreased by 0.09 percentage points per year (P < .001), driven primarily by decreasing mortality in the subgroup not treated in the intensive care unit (ICU) (-0.18 percentage points per year; P < .001). Adjusted annual readmission rates decreased significantly by 0.25 percentage points per year (P < .001). All 7 processes of care were independently associated with reduced 30-day mortality, and 5 were associated with reduced 30-day readmission.
CONCLUSIONS AND RELEVANCE: Performance of processes of care for elderly patients hospitalized for pneumonia improved substantially from 2006 to 2010. Adjusted 30-day mortality declined slightly over time primarily owing to improved survival among non-ICU patients, and all individual processes of care were independently associated with reduced mortality.
Los beneficios de la terapia de combinación macrólido β-lactámicos / más de la terapia β-lactámicos sola para el tratamiento de la neumonía adquirida en la comunidad hospitalizado (CAP) en relación con la gravedad de la neumonía son inciertos. Se estudiaron 5.240 adultos hospitalizados con NAC de 72 fideicomisos de atención secundaria en Inglaterra y Gales. El paciente interno general de 30 días (IP) la tasa de mortalidad fue del 24,4%. La terapia de combinación se prescribió en 3239 (61,8%) pacientes. En un modelo multivariable, el tratamiento combinado se asoció significativamente con una menor de 30 días la tasa de mortalidad IP en pacientes con NAC de gravedad moderada (OR ajustado 0,54; IC del 95%: 0,41 a 0,72) y CAP de alta gravedad (OR ajustada 0,76, IC del 95% 0,60 hasta 0,96), pero no de la PAC bajo la gravedad.
The effects of antibiotic timing on outcomes of patients with community-acquired pneumonia (CAP) are controversial. Moreover, no information is available regarding this issue in healthcare-associated pneumonia (HCAP). We aimed to determine the impact of antibiotic timing on 30-day mortality of patients with CAP and HCAP. Non-immunocompromised adults admitted to hospital through the emergency department (ED) with community-onset pneumonia were prospectively observed from 2001 to 2009. Patients who received prior antibiotics were excluded. Of 1593 patients with pneumonia who were analyzed, 1274 had CAP and 319 HCAP. The mean time from patient arrival at the ED until antibiotic administration was 5.8 h (standard deviation (SD) 3.5) in CAP and 6.1 h (SD 3.8) in HCAP (p 0.30). Mortality was higher in patients with HCAP (5.5% vs. 13.5%; p <0.001). After adjusting for confounding factors in a logistic regression analysis, the antibiotic administration ≤4 h was not associated with decreased 30-day mortality in patients with CAP (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.57-2.21) and in patients with HCAP (OR 0.59, 95% CI 0.19-1.83). Similarly, antibiotic administration ≤8 h was not associated with decreased 30-day mortality in CAP (OR 1.58, 95% CI 0.64-3.88) and HCAP patients (OR 0.59, 95% CI 0.19-1.83). In conclusion, antibiotic administration within 4 or 8 h of arrival at the ED did not improve 30-day survival in hospitalized adults for CAP or HCAP.
BACKGROUND: Although processes of care are common proxies for health care quality, their associations with medical outcomes remain uncertain.
METHODS: For 2076 patients hospitalized with pneumonia from 32 emergency departments, we used multilevel logistic regression modeling to assess independent associations between patient outcomes and the performance of 4 individual processes of care (assessment of oxygenation, blood cultures, and rapid initiation [<4 hours] and appropriate selection of antibiotic therapy) and the cumulative number of processes of care performed.
RESULTS: Overall, 141 patients (6.8%) died. Mortality was 0.3% to 1.7% lower for patients who had each of the individual processes of care performed (P≥.13 for each comparison); mortality was 7.5% for patients who had 0 to 2 processes of care, 7.2% for those with 3 processes of care, and 5.8% for those with all 4 processes of care performed (P=.39). Mortality was not significantly associated with either individual or cumulative process measures in multivariable models.
CONCLUSION: Neither the individual processes of care nor the cumulative number performed is associated with short-term mortality for pneumonia.
OBJECTIVE: In this observational study, we compared the outcomes of moxifloxacin monotherapy as compared to ß-lactam monotherapy as well as ß-lactam combination therapy in patients with community-acquired pneumonia (CAP).
METHODS: Patients recruited within the German Competence Network for CAP (CAPNETZ) were evaluated for treatment regimen. Primary outcome variables were six months overall mortality, pneumonia-related mortality according to clinical judgment and treatment failures (necessity for treatment change and death).
RESULTS: Overall, 4091 patients (mean age 64.4±17.8 (range 18-101) years, 2433 male (59.5%)) were included. 2068 patients received moxifloxacin (n=365) or ß-lactam monotherapy (n=1703). 330 patients died within six months. After controlling for confounders in multivariate analysis, moxifloxacin monotherapy had higher survival as compared to ß-lactam monotherapy (hazard ratio for moxifloxacin 0.57, 95% CI 0.35-0.92). Multivariate analysis including interaction terms showed that the protective effect of moxifloxacin was not present for CRB-65 class 0 but increased with higher CRB-65 scores (HR 0.69, 95% CI 0.50-0.96). Regarding pneumonia-related death, moxifloxacin monotherapy was also protective in multivariate analysis (HR 0.36, 95% CI 0.13-0.99). Moxifloxacin was also significantly associated with less treatment failures (p<0.001). In addition, it was not inferior to combination ß-lactam treatment (p=0.062).
CONCLUSIONS: In CRB-65 class 0 moxifloxacin was equivalent to ß-lactams. Our observations are in support of a use of moxifloxacin monotherapy in hospitalized patients with moderate CAP (CRB-65 classes 1 and 2).
OBJETIVOS: Las directrices recomiendan de doble terapia que consiste en un betalactámico / macrólidos (BLM) para los pacientes hospitalizados con neumonía adquirida en la comunidad. Sin embargo, la superioridad sobre los beta-lactámicos-monoterapia (BL) sigue sin comprobarse.
Se realizaron análisis de un estudio observacional iniciado por la red de competencia alemana CAPNETZ: MÉTODOS.
RESULTADOS: Mil ochocientos cincuenta y cuatro pacientes fueron tratados con BL (49,0%) o BLM (51,0%). Terapia BLM se asoció con una menor mortalidad ajustada 14 días [odds ratio (OR) 0,53; 95% intervalo de confianza (IC): 0,30 a 0,94]. CRB65, enfermedad neoplásica, edad y residencia hogar de ancianos se confirmaron como predictores independientes de muerte. Ajustado el riesgo de mortalidad 14 días se redujo claramente en pacientes con CRB65 = 2 (n = 411; OR 0,35; IC: 0,12 a 0,99) y CRB65> o = 2 (n = 519; OR 0,42; IC: 0,18 hasta 0,997). Sin embargo, esto no se pudo demostrar para ajustada de mortalidad a 30 días. Los pacientes con CRB65 <o = 1 presentaron una mortalidad baja (2,1%), sin la influencia de la BLM. Terapia BLM se asoció con menor riesgo ajustada de fracaso del tratamiento a los 14 días (n = 1,854; OR 0,65; IC: 0,47 a 0,89) y 30 días (OR 0,69; IC: 0,51 hasta 0,94), así como en el subgrupo de pacientes con CRB65 = 2 y CRB65> o = 2.
CONCLUSIONES: Este estudio sugiere la superioridad de la terapia BLM en pacientes con clases de riesgo CRB65 de 2 o mayor en la mortalidad de 14 días. Terapia BLM también se asoció con un menor riesgo de fracaso del tratamiento.
Se evaluó el impacto del cumplimiento de las guías italianas sobre el resultado de la neumonía adquirida en la comunidad hospitalizado (PAC) en los departamentos de medicina interna. Todos los pacientes Bellas clase IV o V de la PAC se incluyeron en este estudio multicéntrico, intervencionista, antes y después, compuesto de tres fases: 1) una fase retrospectiva (RP; 1.443 pacientes); 2) una fase de implantación de la Guía; y 3) una fase prospectivo (PP; 1404 pacientes). Prescripción antibióticos de acuerdo con las directrices aumentó significativamente en el PP. El riesgo de fracaso al final de la terapia de primera línea fue significativamente menor en el PP contra el RP (odds ratio (OR) 0,83; intervalo de confianza del 95% (IC) 0,69 a 1,00), especialmente en pacientes de clase V Bellas (OR 0,71; 95% CI 0,51 a 0,98). Análisis de los resultados en la población general (2.847 pacientes) mostró una ventaja estadísticamente significativa para compatible versus tratamientos no compatibles en términos de tasa de fracaso (OR 0,74; IC 95% 0,60-0,90) y una ventaja en términos de mortalidad (OR 0.77, 95% CI 0,58 a 1,04). Monoterapia cefalosporina antineumocócica se asoció con una baja tasa de éxito (68,6%) y la mortalidad más alta (16,2%); levofloxacino solo y la combinación de cefalosporina y macrólido resultaron en tasas más altas de éxito (79,1 y 76,7%, respectivamente) y la mortalidad significativamente más bajas (9,1 y 5,7%, respectivamente). En general, se obtuvo un bajo cumplimiento de las directrices en la fase prospectiva (44%), lo que indica la necesidad de un futuro más agresivo y enfoques proactivos.
ANTECEDENTES: Directrices para el tratamiento empírico de los pacientes hospitalizados con neumonía proporcionan recomendaciones específicas para la selección de antibióticos que se basa principalmente en los resultados de estudios observacionales.
Métodos: Se realizó un estudio retrospectivo de 27.330 viven en la comunidad, los pacientes inmunocompetentes Medicare (edad,> 65 años) con neumonía que fueron hospitalizados en 1998-1999 y 2000-2001. Las asociaciones entre regímenes antimicrobianos iniciales y la mortalidad ajustada por riesgo se evaluaron, cuenta las diferencias en las características del paciente, comorbilidades, gravedad de la enfermedad, la ubicación geográfica y los procesos de atención. El tratamiento con monoterapia nonpseudomonal cefalosporina de tercera generación constituía el grupo de referencia para las comparaciones.
RESULTADOS: En los pacientes no en la unidad de cuidados intensivos, el tratamiento inicial con monoterapia fluoroquinolona se asoció con una reducción de la mortalidad en la mortalidad hospitalaria, de 14 días, y las tasas de mortalidad a los 30 días (odds ratio ajustada [AOR] para la mortalidad a 30 días, 0,7 ; intervalo de confianza del 95% [IC]: 0,6 a 0,9; P = 0,001). La combinación de una cefalosporina más un macrólido se asoció con tasas reducidas de 14 días y 30 días de mortalidad (AOR para la mortalidad a los 30 días, 0,7; IC del 95%, 0,6-0,9; p <0,001). Para pacientes de cuidados intensivos, la combinación de una cefalosporina y un macrólido se asoció con una reducción de la mortalidad hospitalaria (AOR, 0,6; IC del 95%, 0,3-0,9; p = 0,018).
Conclusiones: El tratamiento antimicrobiano inicial con la combinación de una cefalosporina de segunda o tercera generación y un macrólido o el tratamiento inicial con una fluoroquinolona se asoció con una tasa de reducción de la mortalidad de 30 días, en comparación con el tratamiento con monoterapia cefalosporina de tercera generación, entre los no- pacientes de cuidados intensivos. Aunque nuestros resultados son consistentes con otros estudios observacionales, la controversia continúa existiendo sobre el uso de los estudios de cohorte no experimentales para demostrar asociaciones entre los procesos de atención, tales como la selección de antibióticos, y los resultados del paciente.
The choice of empirical antibiotic treatment for patients with clinically suspected community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. We compared strategies of empirical treatment (allowing deviations for medical reasons) with beta-lactam monotherapy, beta-lactam-macrolide combination therapy, or fluoroquinolone monotherapy.
METHODS:
In a cluster-randomized, crossover trial with strategies rotated in 4-month periods, we tested the noninferiority of the beta-lactam strategy to the beta-lactam-macrolide and fluoroquinolone strategies with respect to 90-day mortality, in an intention-to-treat analysis, using a noninferiority margin of 3 percentage points and a two-sided 90% confidence interval.
RESULTS:
A total of 656 patients were included during the beta-lactam strategy periods, 739 during the beta-lactam-macrolide strategy periods, and 888 during the fluoroquinolone strategy periods, with rates of adherence to the strategy of 93.0%, 88.0%, and 92.7%, respectively. The median age of the patients was 70 years. The crude 90-day mortality was 9.0% (59 patients), 11.1% (82 patients), and 8.8% (78 patients), respectively, during these strategy periods. In the intention-to-treat analysis, the risk of death was higher by 1.9 percentage points (90% confidence interval [CI], -0.6 to 4.4) with the beta-lactam-macrolide strategy than with the beta-lactam strategy and lower by 0.6 percentage points (90% CI, -2.8 to 1.9) with the fluoroquinolone strategy than with the beta-lactam strategy. These results indicated noninferiority of the beta-lactam strategy. The median length of hospital stay was 6 days for all strategies, and the median time to starting oral treatment was 3 days (interquartile range, 0 to 4) with the fluoroquinolone strategy and 4 days (interquartile range, 3 to 5) with the other strategies.
CONCLUSIONS:
Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality. (Funded by the Netherlands Organization for Health Research and Development; CAP-START ClinicalTrials.gov number, NCT01660204.).
