Medline ® Abstracts for References 52-54
of 'Treatment of community-acquired pneumonia in adults who require hospitalization'
Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia.
Restrepo MI, Mortensen EM, Waterer GW, Wunderink RG, Coalson JJ, Anzueto A
Eur Respir J. 2009;33(1):153. Epub 2008 Sep 3.
Recent studies suggest that macrolides may have beneficial effects for patients at risk for certain infections. The current authors examined the effect of macrolide therapy on 30- and 90-day mortality for patients with severe sepsis caused by pneumonia. A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had chest radiography consistent with, and had a discharge diagnosis of pneumonia and clinical criteria of severe sepsis. Subjects were considered to be on macrolides if they received at least one dose within 48 h of admission. Severe sepsis was present in 237 (30.1%) subjects, out of whom 104 (43.9%) received macrolides. Mortality was 20.3% at 30 days and 24.5% at 90 days. In the multivariable analysis, the use of macrolide was associated with decreased mortality at 30 days (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.2-0.7) and at 90 days (HR 0.3, 95% CI 0.2-0.6) in patients with severe sepsis and in patients with macrolide-resistant pathogens (HR 0.1, 95% CI 0.02-0.5). Macrolide use was associated with decreased mortality in patients with severe sepsis due to pneumonia and macrolide-resistant pathogens. Confirmatory studies are needed to determine whether macrolide therapy may be protective for patients with sepsis.
Veterans Evidence-Based Research Dissemination Implementation Center, Audie L. Murphy Veterans Affairs Hospital, San Antonio, TX, USA. email@example.com
Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia.
Martin-Loeches I, Lisboa T, Rodriguez A, Putensen C, Annane D, Garnacho-Montero J, Restrepo MI, Rello J
Intensive Care Med. 2010;36(4):612. Epub 2009 Dec 2.
OBJECTIVE: To assess the effect on survival of macrolides or fluoroquinolones in intubated patients admitted to the intensive care unit (ICU) with severe community-acquired pneumonia (severe CAP).
METHODS: Prospective, observational cohort, multicenter study conducted in 27 ICUs of 9 European countries. Two hundred eighteen consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of CAP were recruited.
RESULTS: Severe sepsis and septic shock were present in 165 (75.7%) patients. Microbiological documentation was obtained in 102 (46.8%) patients. ICU mortality was 37.6% (n = 82). Non-survivors were older (58.6 +/- 16.1 vs. 63.4 +/- 16.7 years, P<0.05) and presented a higher score on the simplified Acute Physiology Score II at admission (45.6 +/- 15.4 vs. 50.8 +/- 17.5, P<0.05). Monotherapy was given in 43 (19.7%) and combination therapy in 175 (80.3%) patients. Empirical antibiotic therapy was in accordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines in 100 (45.9%) patients (macrolides in 46 patients and fluoroquinolones in 54). In this cohort, a Cox regression analysis adjusted by severity identified that macrolide use was associated with lower ICU mortality (hazard ratio, HR 0.48, confidence intervals, 95% CI 0.23-0.97, P = 0.04) when compared to the use of fluoroquinolones. When more severe patients presenting severe sepsis and septic shock were analyzed (n = 92), similar results were obtained (HR 0.44, 95% CI 0.20-0.95, P = 0.03).
CONCLUSIONS: Patients with severe community-acquired pneumonia had a low adherence with the 2007 IDSA/ATS guidelines. Combination therapy with macrolides should be preferred in intubated patients with severe CAP.
Critical Care Department, Mater Misericordiae University Hospital, Dublin, Ireland.
Antibiotic treatment strategies for community-acquired pneumonia in adults.
Postma DF, van Werkhoven CH, van Elden LJ, Thijsen SF, Hoepelman AI, Kluytmans JA, Boersma WG, Compaijen CJ, van der Wall E, Prins JM, Oosterheert JJ, Bonten MJ, CAP-START Study Group
N Engl J Med. 2015;372(14):1312.
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.).
From the Julius Center for Health Sciences and Primary Care (D.F.P., C.H.W., M.J.M.B.) and the Departments of Internal Medicine and Infectious Diseases (D.F.P., A.I.M.H., J.J.O.) and Medical Microbiology (M.J.M.B.), University Medical Center Utrecht, and the Departments of Internal Medicine (D.F.P.), Pulmonology (L.J.R.E.), and Medical Microbiology (S.F.T.T.), Diakonessenhuis Utrecht, Utrecht, the Department of Medical Microbiology, Amphia Ziekenhuis Breda, Breda (J.A.J.W.K.), the Department of Pulmonology, Medisch Centrum Alkmaar, Alkmaar (W.G.B.), the Department of Internal Medicine, Kennemer Gasthuis Haarlem, Haarlem (C.J.C.), the Department of Pulmonology, Spaarne Ziekenhuis, Hoofddorp (E.W.), and the Department of Internal Medicine, Academic Medical Center Amsterdam, Amsterdam (J.M.P.) - all in the Netherlands.