Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia

Introduction Combination antibiotic therapy for ventilator
associated pneumonia (VAP) is often used to broaden the
spectrum of activity of empirical treatment. The relevance of
such synergy is commonly supposed but poorly supported. The
aim of the present study was to compare the clinical outcome
and the course of biological variables in patients treated for a
VAP, using a monotherapy with a beta-lactam versus a
combination therapy.
Methods Patients with VAP were prospectively randomised to
receive either cefepime alone or cefepime in association with
amikacin or levofloxacin. Clinical and inflammatory parameters
were measured on the day of inclusion and thereafter.
Results Seventy-four mechanically ventilated patients meeting
clinical criteria for VAP were enrolled in the study. VAP was
microbiologically confirmed in 59 patients (84%). Patients were
randomised to receive cefepime (C group, 20 patients),
cefepime with amikacin (C-A group, 19 patients) or cefepime
with levofloxacin (C-L group, 20 patients). No significant
difference was observed regarding the time course of
temperature, leukocytosis or C-reactive protein level. There
were no differences between length of stay in the intensive care
unit after infection, nor in ventilator free days within 28 days after
infection. No difference in mortality was observed.
Conclusion Antibiotic combination using a fourth generation
cephalosporin with either an aminoside or a fluoroquinolone is
not associated with a clinical or biological benefit when
compared to cephalosporin monotherapy against common
susceptible pathogens causing VAP.