Two retrospective studies (1,2) and a prospective study (3) have observed a lower mortality in patients with community-acquired bacteraemic pneumococcal pneumonia treated with combination therapy compared with subjects treated with only one antimicrobial
One retrospective study (4) concluded that combination antibiotic therapy does not decrease mortality in patients with severe pneumococcal infection
( 1) Arch Inter Med 2001; 161: 1837-1842 (3) Am J Resp Crit Care Med 2004; 170: 440-444. (2) Clin Infect Dis 2003; 36: 389-395. (4) Eur J Clin Microbiol Infect Dis. 2005; 24: 688-690.
Prospective, randomized 1:1, comparative, open trial
398 randomized patients who had been admitted to the ICU with severe CAP without shock.
Combination therapy: Cefotaxime plus ofloxacin
Clinical efficacy, bacteriologic response and mortality was similar in both group
Chest. 2005; 128:172-183.
Patients on MV Although in patients on MV, the cure rate and overall mortality rates were not statistically different in both treatment groups, the noninferiority of L to C + O could not be demostrated. Chest. 2005; 128:172-183.
Β -lactam and Macrolide Combination Therapy vs. Fluoroquinolone Monotherapy BL+M F BL+M F Antimicrob Agents Chemother 2007; 51: 3977-3982. 0 30 50 10 20 40 Mortality (%) PSI 4 PSI 5 p=0.6 p=0.05
What agents? Macrolides or fluoroquinolones? That’s the question .
172 episodes of severe CAP Multivariate analysis. 30-day Mortality B-lact+fluoroq OR 2.71 (95%IC 1.2-6.1)
No previous study has been designed to determine the optimal duration of combination therapy
Current guidelines do not establish duration of combination therapy
Once the etiology of CAP has been identified on the basis of reliable microbiological methods, antimicrobial therapy should be directed at that pathogen. (Moderate recommendation; level III evidence.IDSA)
“ If our conclusions are confirmed by other prospective studies, we recommend that clinicians target combination antibiotic treatment only for those patients who are critically ill, and limit the duration of the combination to 3–5 days ”.
Delay of antimicrobial therapy and mortality Arch Intern Med 2004; 164: 637-644
Kumar, et al. Crit Care Med 2006;34:1589–1596 Risk of death with increasing antimicrobial delay: subgroups X, delay (hours) Adjusted odds ratio of death 1.0 1.1 1.2 1.3 All Documented Suspected Culture + Culture - Bacteraemia + Bacteraemia - Community Nosocomial Gram + Gram - Fungal Respiratory Urinary tract Intra-abdominal Skin/soft tissue 1385 769 608 1546 459 1695 2154 N 912 1242 768 584 838 131 230 156 641