title: Meropenem versus imipenem/cilastatin as empirical monotherapy for serious bacterial infections in the intensive care unit.
abstract: OBJECTIVE
  To compare the efficacy and tolerability of meropenem and imipenem/cilastatin as empirical monotherapy in intensive care unit (ICU) patients with serious bacterial infections.
  
  
  METHODS
  A multicenter, open-label, randomized, parallel-group trial was conducted in Belgium, evaluating empirical monotherapy with meropenem or imipenem/cilastatin (both 1 g/8 h intravenously) in ICU patients with one or more of the following infections caused by sensitive pathogens: lower respiratory tract infection (LRTI) in ventilated patients, intra-abdominal infection or sepsis.
  
  
  RESULTS
  The overall satisfactory clinical response rate at the end of randomized treatment was 77.0% (67/87) with meropenem and 68.1% (62/91) with imipenem/cilastatin (difference 8.9%; 95% confidence interval -4.2% to 21.9%; P = 0.185). The two drugs produced similar satisfactory clinical response rates against LRTIs: 68.3% (41/60) with meropenem versus 68.6% (35/51) with imipenem/cilastatin. Meropenem appeared to be slightly more effective against intra-abdominal infections: 95.5% (21/22) versus 76.7% (23/30), respectively. All five meropenem recipients with sepsis had a satisfactory clinical response, compared to 40.0% (4/10) of those who received imipenem/cilastatin. The overall satisfactory bacteriologic response rate was 67.1% (49/73) with meropenem and 60.3% (44/73) with imipenem/cilastatin (difference 6.9%; 95% confidence interval -8.7% to 22.4%; P = 0.389). The predominant pathogens were Escherichia coli, Enterobacter spp. and Pseudomonas aeruginosa. No incidences of drug-related nausea and vomiting were reported, but one probable drug-related seizure occurred in the imipenem/cilastatin group.
  
  
  CONCLUSIONS
  Meropenem is at least as efficacious (clinically and bacteriologically) as imipenem/cilastatin for the empirical monotherapy of serious bacterial infections in ICU patients, and it can therefore be considered a useful option in this setting. Moreover, meropenem is well tolerated and offers several potential advantages, including greater in vitro activity against Gram-negative pathogens and the option of bolus administration.
authors.affiliation: Department of Intensive Care Medicine, University Hospital Gasthuisberg, Leuven, Belgium. Charles.Verwaest@uz.kuleuven.ac.be
authors.forename: C
authors.initials: C
authors.lastname: Verwaest
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D001530:Belgium; D015377:Cilastatin / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D013845:Thienamycins / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D011480:Protease Inhibitors; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D000077731:Meropenem