Levofloxacin in the empirical treatment of patients with suspected bacteraemia/sepsis: comparison with imipenem/cilastatin in an open, randomized trial.
An open, randomized, multinational, multicentre study was conducted to compare the efficacy, safety and tolerability of levofloxacin 500 mg twice daily with imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized adult patients with clinically suspected bacteraemia/ sepsis. Levofloxacin patients could change from iv to oral administration after a minimum of 48 h iv treatment if clinical signs and symptoms of sepsis had improved. The primary efficacy analysis was based on the clinical and bacteriological response at clinical endpoint. A total of 503 patients were randomized and 499 included in the intent-to-treat population. The per-protocol population comprised 287 patients with bacteriologically proven infection. Clinical cure rates at clinical endpoint in the intent-to-treat population and per-protocol population were 77% (184/239) and 89% (125/140), respectively, for levofloxacin and 68% (178/260) and 85% (125/147), respectively, for imipenem/cilastatin. At follow-up, the cure rates in the per-protocol population were 84% for levofloxacin and 69% for imipenem/cilastatin. The 95% confidence interval for both populations showed that levofloxacin was as effective as imipenem/cilastatin. A satisfactory bacteriological response was obtained in 87% (96/110) of levofloxacin patients and 84% (97/116) of imipenem/cilastatin patients at clinical endpoint. Adverse events possibly related to the study drug were reported in 74 (31%) levofloxacin patients and 79 (30%) imipenem/cilastatin patients. There were no clinically appreciable differences between the treatment groups. Levofloxacin 500 mg twice daily, either iv or as sequential iv/oral therapy, was as effective and well tolerated as imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized patients with suspected bacteraemia/sepsis.
Geddes
A
A
Department of Infectious Diseases, University of Birmingham Medical School, Edgbaston, Birmingham, UK. geddesam@birmingham.ac.uk
Thaler
M
M
Schonwald
S
S
Härkönen
M
M
Jacobs
F
F
Nowotny
I
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D015377:Cilastatin / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D064704:Levofloxacin; D008875:Middle Aged; D015242:Ofloxacin / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013845:Thienamycins / Q000627:therapeutic use
D000890:Anti-Infective Agents; D004338:Drug Combinations; D011480:Protease Inhibitors; D013845:Thienamycins; D015377:Cilastatin; D064704:Levofloxacin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D015242:Ofloxacin