Abstract
A cohort of 1,391 patients with community-acquired pneumonia of unknown etiology, atypical pneumonia, Legionella pneumophila pneumonia, viral pneumonia, or pneumococcal pneumonia was studied according to a standard protocol to analyse whether the addition of a macrolide to β-lactam empirical treatment decreases mortality rates. Patients admitted to the intensive care unit were excluded. Severity was assessed using the PORT score. An etiological diagnosis was achieved in 498 (35.8%) patients (292 infections due to Streptococcus pneumoniae). Treatment was chosen by the attending physician according to his/her own criteria: β-lactam agent in 270 and β-lactam agent plus a macrolide in 918 cases. The mortality rate was 13.3% in the group treated with a β-lactam agent alone and 6.9% in the group treated with a β-lactam agent plus a macrolide (p=0.001). The percentage of PORT-group V patients was 32.6% in the group treated with a beta-lactam agent alone compared to 25.7% in the group who received a β-lactam agent plus a macrolide (p=0.02). After controlling for PORT score, the odds of fatal outcome was two times higher in patients treated with a beta-lactam agent alone than in those treated with a β-lactam agent plus a macrolide (adjusted OR = 2, 95%CI 1.24–3.23). The results suggest that the addition of a macrolide to an initial β-lactam-based antibiotic regimen is associated with lower mortality in patients with community-acquired pneumonia, independent of severity of infection, thus supporting the recommendation of a β-lactam-agent plus a macrolide as empirical therapy.
Similar content being viewed by others
References
Barlett JG, Mundy LM (1995) Community-acquired pneumonia. N Engl J Med 333:1618–1624
Fine MJ, Smith MA, Carson CA, Mutha SS, Sankey SS, Weissfeld LA, Kapoor WN (1996) Prognosis and outcomes of patients with community-acquired pneumonia. JAMA 275:134–141
Mandell LA, Marrie TJ, Grossman RF, Chow AW, Hyland RH (2000) Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis 31:383–421
Niederman MS, Mandell LA, Anzueto A, et al (2001) Guidelines for the management of adults with CAP. Diagnosis, assessment of severity, antimicrobial therapy and prevention. Am J Respir Crit Care Med 163:1730–1754
Macfarlane JT (2001) BTS guidelines for the management of CAP in adults. Thorax 56(Suppl 4):iv1–iv64
Gleason PP, Meehan TP, Fine JM, Galusha DH, Fine MJ (1999) Association between initial antimicrobial therapy and medical outcomes for hospitalised elderly patients with pneumonia. Arch Intern Med 159:2562–2572
Stahl JE, Barza M, DesJardin J, Martin R, Eckman MH (1999) Effect of macrolides as part of initial empirical therapy on length of stay in patients hospitalized with community-acquired pneumonia. Arch Intern Med 159:2576–2580
Dudas V, Hopefl A, Jacobs R, Guglielmo BJ (2000) Antimicrobial selection for hospitalized patients with presumed community-acquired pneumonia: a survey of nonteaching U.S. community hospitals. Ann Pharmacother 34:446–452
Houck PM, MacLehose RF, Niederman MS, Lowery JK (2001) Empiric antibiotic therapy and mortality among Medicare pneumonia inpatients in 10 western states. Chest 119:1420–1426
Mufson MA, Stanek RJ (1999) Bacteremic pneumococcal pneumonia in one American city: a 20-year longitudinal study, 1978–1997. Am J Med 107(Suppl 1A):34–43
Waterer GW, Somes GW, Wunderink RG (2001) Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med 161:1837–1842
Martínez JA, Horcajada JP, Almela M, et al (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 Inf Dis 36:389–395
Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN (1997) A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 336:243–250
Ruiz M, Ewig S, Marcos MA, Martínez JA, Arancibia F, Mensa J, Torres A (1999) Etiology of community-acquired pneumonia: impact of age, comorbidity and severity. Am J Respir Crit Care Med 160:397–405
García Vázquez E, Martínez JA, Mensa J, Sánchez F, Marcos MA, de Roux A, Torres A (2003) C-reactive protein levels in community-acquired pneumonia. Eur Respir J 21:702–705
Porath A, Schlaeffer F, Pick N, Leinonen M, Lieberman D (1997) Pneumococcal community-acquired pneumonia in 148 hospitalized adult patients. Eur J Clin Microbiol Infect Dis 16:863–870
Lieberman D, Schlaeffer F, Boldur I, et al (1996) Multiple pathogens in adult patients admitted with CAP: a one-year prospective study of 346 consecutive patients. Thorax 51:179–184
Mundy LM, Oldach D, Auwaerter PG, et al (1998) Implications for macrolide treatment in community-acquired pneumonia. Chest 113:1201–1206
Johansen HK, Jensen TG, Dessau RB, Lundgren B, Frimodt-Moller N (2000) Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo. J Antimicrob Chemother 46:973–980
Ortega M, Marco F, Soriano A, Gómez J, Almela M, Mensa J (2004) In vitro antagonism between β-lactam and macrolide in Streptococcus pneumoniae. How important is the antibiotic order? Int J Antimicrob Agents 24:178–180
Jaffé A, Bush A (2001) Anti-inflammatory effects of macrolides in lung diseases. Pediatr Pulmonol 31:464–473
Wales D, Woodhead M (1999) The anti-inflammatory effects of macrolides. Thorax 54(Suppl 2):S58–S62
Culic O, Erakovic V, Cepelak I, et al (2002) Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects. Eur J Pharmacol 450:277–289
Stuertz K, Schmidt H, Eiffert H, Schwartz P, Mader M, Nau R (1998) Differential release of lipoteichoic acids from S. pneumoniae as a result of exposure to beta-lactam, rifamycins, trovafloxacin and quinupristin-dalfopristin. Antimicrob Agents Chemother 42:277–281
Wang E, Simard M, Ouellet N, Bergeron Y, Beauchamp D, Bergeron MG (2000) Modulation of cytokines and chemokines, limited pulmonary vascular bed permeability and prevention of septicemia and death with ceftriaxone and itnerleukin-10 in pneumococcal pneumonia. J Infect Dis 182:1255–1259
Rello J, Rodriguez R, Jubert P, Alvarez B(1996) Severe CAP in the elderly: epidemiology and prognosis. Clin Infect Dis 23:723–728
Acknowledgement
This study was supported by RED GIRA and RED RESPIRA, Instituto Carlos III.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
García Vázquez, E., Mensa, J., Martínez, J.A. et al. 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, 190–195 (2005). https://doi.org/10.1007/s10096-005-1295-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-005-1295-9