title: Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group.
abstract: Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.
authors.affiliation: Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: M P
authors.initials: MP
authors.lastname: Fink
authors.forename: D R
authors.initials: DR
authors.lastname: Snydman
authors.forename: M S
authors.initials: MS
authors.lastname: Niederman
authors.forename: K V
authors.initials: KV
authors.lastname: Leeper
authors.forename: R H
authors.initials: RH
authors.lastname: Johnson
authors.forename: S O
authors.initials: SO
authors.lastname: Heard
authors.forename: R G
authors.initials: RG
authors.lastname: Wunderink
authors.forename: J W
authors.initials: JW
authors.lastname: Caldwell
authors.forename: J J
authors.initials: JJ
authors.lastname: Schentag
authors.forename: G A
authors.initials: GA
authors.lastname: Siami
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015377:Cilastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077728:Cilastatin, Imipenem Drug Combination; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D005260:Female; D006760:Hospitalization; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D011552:Pseudomonas Infections / Q000150:complications; D011550:Pseudomonas aeruginosa; D012044:Regression Analysis; D012640:Seizures / Q000150:complications
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D002939:Ciprofloxacin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination