Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia
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).
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.
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).
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.
KeywordsSevere community-acquired pneumonia Macrolides Critical care Mortality
The EU-VAP/CAP Study is endorsed by the European Critical Care Research Network (ECCRN). This study has been supported in part by grants from CIBER Enfermedades Respiratorias (CIBERES 37706/06/0036) by Carlos III Health Institute and FISS 04/1500. Dr. Restrepo is supported by a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant and National Health Institute grant KL2 RR025766.
Conflict of interest statement
The authors declare no conflict of interest regarding this manuscript.
- 2.Bodi M, Rodriguez A, Sole-Violan J, Gilavert MC, Garnacho J, Blanquer J, Jimenez J, de la Torre MV, Sirvent JM, Almirall J, Doblas A, Badia JR, Garcia F, Mendia A, Jorda R, Bobillo F, Valles J, Broch MJ, Carrasco N, Herranz MA, Rello J (2005) Antibiotic prescription for community-acquired pneumonia in the intensive care unit: impact of adherence to Infectious Diseases Society of America guidelines on survival. Clin Infect Dis 41:1709–1716CrossRefPubMedGoogle Scholar
- 3.Shorr AF, Bodi M, Rodriguez A, Sole-Violan J, Garnacho-Montero J, Rello J, for the CAPUCI Study Investigators (2006) Impact of antibiotic guideline compliance on duration of mechanical ventilation in critically ill patients with community-acquired pneumonia. Chest 130:93–100CrossRefPubMedGoogle Scholar
- 5.Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG (2007) Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(Suppl 2):S27–S72CrossRefPubMedGoogle Scholar
- 7.Giamarellos-Bourboulis EJ, Adamis T, Laoutaris G, Sabracos L, Koussoulas V, Mouktaroudi M, Perrea D, Karayannacos PE, Giamarellou H (2004) Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant pseudomonas aeruginosa. Antimicrob Agents Chemother 48:93–99CrossRefPubMedGoogle Scholar
- 8.Garcia Vazquez E, Mensa J, Martinez JA, Marcos MA, Puig J, Ortega M, Torres A (2005) Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone. Eur J Clin Microbiol Infect Dis 24:190–195CrossRefPubMedGoogle Scholar
- 11.Koulenti D, Lisboa T, Brun-Buisson C, Krueger W, Macor A, Sole-Violan J, Diaz E, Topeli A, DeWaele J, Carneiro A, Martin-Loeches I, Armaganidis A, Rello J (2009) The spectrum of practice in the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation in European ICUs. Crit Care Med 37:2360–2368CrossRefPubMedGoogle Scholar
- 15.Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS.CCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250-1256Google Scholar
- 18.Weiss K, Low DE, Cortes L, Beaupre A, Gauthier R, Gregoire P, Legare M, Nepveu F, Thibert D, Tremblay C, Tremblay J (2004) Clinical characteristics at initial presentation and impact of dual therapy on the outcome of bacteremic Streptococcus pneumoniae pneumonia in adults. Can Respir J 11:589–593PubMedGoogle Scholar
- 20.Baddour LM, Yu VL, Klugman KP, Feldman C, Ortkvist A, Rello J, Morris AJ, Luna CM, Snydman DR, Ko WC, Chedid BF, Hui DS, Andremont A, Chiou CCC, the International Pneumococcal Study Group (2004) Combination antibiotic therapy may lower mortality in severely ill patients with Streptococcus pneumoniae bacteremia. Am J Respir Crit Care Med 170:400–404CrossRefGoogle Scholar
- 21.Martinez JA, Horcajada JP, Almela M, Marco F, Soriano A, Garcia E, Marco MA, Torres A, Mensa J (2003) Addition of a macrolide to a beta-lactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia. Clin Infect Dis 36:389–395CrossRefPubMedGoogle Scholar