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Antimicrob Agents Chemother. Mar 1994; 38(3): 547–557.
PMCID: PMC284496

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.


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.

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  • Arcieri GM, Becker N, Esposito B, Griffith E, Heyd A, Neumann C, O'Brien B, Schacht P. Safety of intravenous ciprofloxacin. A review. Am J Med. 1989 Nov 30;87(5A):92S–97S. [PubMed]
  • Bayer AS. Clinical utility of new quinolones in treatment of osteomyelitis and lower respiratory tract infections. Eur J Clin Microbiol Infect Dis. 1989 Dec;8(12):1102–1110. [PubMed]
  • Beam TR, Jr, Gilbert DN, Kunin CM. General guidelines for the clinical evaluation of anti-infective drug products. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis. 1992 Nov;15 (Suppl 1):S5–32. [PubMed]
  • Celis R, Torres A, Gatell JM, Almela M, Rodríguez-Roisin R, Agustí-Vidal A. Nosocomial pneumonia. A multivariate analysis of risk and prognosis. Chest. 1988 Feb;93(2):318–324. [PubMed]
  • Chastre J, Viau F, Brun P, Pierre J, Dauge MC, Bouchama A, Akesbi A, Gibert C. Prospective evaluation of the protected specimen brush for the diagnosis of pulmonary infections in ventilated patients. Am Rev Respir Dis. 1984 Nov;130(5):924–929. [PubMed]
  • Chow AW, Hall CB, Klein JO, Kammer RB, Meyer RD, Remington JS. Evaluation of new anti-infective drugs for the treatment of respiratory tract infections. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis. 1992 Nov;15 (Suppl 1):S62–S88. [PubMed]
  • Craig CP, Connelly S. Effect of intensive care unit nosocomial pneumonia on duration of stay and mortality. Am J Infect Control. 1984 Aug;12(4):233–238. [PubMed]
  • Craven DE, Kunches LM, Kilinsky V, Lichtenberg DA, Make BJ, McCabe WR. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am Rev Respir Dis. 1986 May;133(5):792–796. [PubMed]
  • Fagon JY, Chastre J, Domart Y, Trouillet JL, Pierre J, Darne C, Gibert C. Nosocomial pneumonia in patients receiving continuous mechanical ventilation. Prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques. Am Rev Respir Dis. 1989 Apr;139(4):877–884. [PubMed]
  • Fagon JY, Chastre J, Hance AJ, Guiguet M, Trouillet JL, Domart Y, Pierre J, Gibert C. Detection of nosocomial lung infection in ventilated patients. Use of a protected specimen brush and quantitative culture techniques in 147 patients. Am Rev Respir Dis. 1988 Jul;138(1):110–116. [PubMed]
  • Faling LJ. New advances in diagnosing nosocomial pneumonia in intubated patients. Part I. Am Rev Respir Dis. 1988 Feb;137(2):253–255. [PubMed]
  • Fernández-Guerrero M, Gudiol F, Rodriguez-Torres A, Arnau C, Valdés L, Vallvé C. Nosocomial pneumonia: comparative multicentre trial between monotherapy with cefotaxime and treatment with antibiotic combinations. Infection. 1991;19 (Suppl 6):S320–S325. [PubMed]
  • Garber GE, Auger P, Chan RM, Conly JM, Shafran SD, Gerson M. A multicenter, open comparative study of parenteral cefotaxime and ceftriaxone in the treatment of nosocomial lower respiratory tract infections. Diagn Microbiol Infect Dis. 1992 Jan;15(1):85–88. [PubMed]
  • Gentry LO, Rodriguez-Gomez G, Kohler RB, Khan FA, Rytel MW. Parenteral followed by oral ofloxacin for nosocomial pneumonia and community-acquired pneumonia requiring hospitalization. Am Rev Respir Dis. 1992 Jan;145(1):31–35. [PubMed]
  • Gleeson K, Reynolds HY. Pneumonia in the intensive care unit setting. J Intensive Care Med. 1992 Jan-Feb;7(1):24–35. [PubMed]
  • Gudiol F, Cabellos C, Pallares R, Linares J, Ariza J. Intravenous ciprofloxacin therapy in severe infections. Am J Med. 1989 Nov 30;87(5A):221S–224S. [PubMed]
  • Haley RW, Culver DH, White JW, Morgan WM, Emori TG. The nationwide nosocomial infection rate. A new need for vital statistics. Am J Epidemiol. 1985 Feb;121(2):159–167. [PubMed]
  • Hartenauer U, Weilemann LS, Bodmann KF, Ritzerfeld WW, Asmus S, Koch EM. Comparative clinical trial of ceftazidime and imipenem/cilastatin in patients with severe nosocomial pneumonias and septicaemias. J Hosp Infect. 1990 Apr;15 (Suppl A):61–64. [PubMed]
  • Hilf M, Yu VL, Sharp J, Zuravleff JJ, Korvick JA, Muder RR. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med. 1989 Nov;87(5):540–546. [PubMed]
  • Hirata-Dulas CA, Stein DJ, Guay DR, Gruninger RP, Peterson PK. A randomized study of ciprofloxacin versus ceftriaxone in the treatment of nursing home-acquired lower respiratory tract infections. J Am Geriatr Soc. 1991 Oct;39(10):979–985. [PubMed]
  • Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818–829. [PubMed]
  • LaForce FM. Systemic antimicrobial therapy of nosocomial pneumonia: monotherapy versus combination therapy. Eur J Clin Microbiol Infect Dis. 1989 Jan;8(1):61–68. [PubMed]
  • Leo RJ, Ballow CH. Seizure activity associated with imipenem use: clinical case reports and review of the literature. DICP. 1991 Apr;25(4):351–354. [PubMed]
  • Leu HS, Kaiser DL, Mori M, Woolson RF, Wenzel RP. Hospital-acquired pneumonia. Attributable mortality and morbidity. Am J Epidemiol. 1989 Jun;129(6):1258–1267. [PubMed]
  • Lode H, Wiley R, Höffken G, Wagner J, Borner K. Prospective randomized controlled study of ciprofloxacin versus imipenem-cilastatin in severe clinical infections. Antimicrob Agents Chemother. 1987 Oct;31(10):1491–1496. [PMC free article] [PubMed]
  • Mangi RJ, Peccerillo KM, Ryan J, Berenson C, Greco T, Thornton G, Andriole VT. Cefoperazone versus ceftriaxone monotherapy of nosocomial pneumonia. Diagn Microbiol Infect Dis. 1992 Jul;15(5):441–447. [PubMed]
  • Mangi RJ, Ryan J, Berenson C, Greco T, Simms M, 3rd, Thornton G, Andriole VT. Cefoperazone versus ceftazidime monotherapy of nosocomial pneumonia. Am J Med. 1988 Jul 25;85(1A):44–48. [PubMed]
  • MANTEL N, HAENSZEL W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959 Apr;22(4):719–748. [PubMed]
  • Martin C, Gouin F, Fourrier F, Junginger W, Prieur BL. Pefloxacin in the treatment of nosocomial lower respiratory tract infections in intensive care patients. J Antimicrob Chemother. 1988 Jun;21(6):795–799. [PubMed]
  • Neu HC, Labthavikul P. Comparative in vitro activity of N-formimidoyl thienamycin against gram-positive and gram-negative aerobic and anaerobic species and its beta-lactamase stability. Antimicrob Agents Chemother. 1982 Jan;21(1):180–187. [PMC free article] [PubMed]
  • Niederman MS. Diagnosing nosocomial pneumonia: to brush or not to brush. J Intensive Care Med. 1991 Jul-Aug;6(4):151–152. [PubMed]
  • Niederman MS, Ferranti RD, Zeigler A, Merrill WW, Reynolds HY. Respiratory infection complicating long-term tracheostomy. The implication of persistent gram-negative tracheobronchial colonization. Chest. 1984 Jan;85(1):39–44. [PubMed]
  • Pachon J, Prados MD, Capote F, Cuello JA, Garnacho J, Verano A. Severe community-acquired pneumonia. Etiology, prognosis, and treatment. Am Rev Respir Dis. 1990 Aug;142(2):369–373. [PubMed]
  • Peloquin CA, Cumbo TJ, Nix DE, Sands MF, Schentag JJ. Evaluation of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections. Impact of plasma concentrations, organism, minimum inhibitory concentration, and clinical condition on bacterial eradication. Arch Intern Med. 1989 Oct;149(10):2269–2273. [PubMed]
  • Potgieter PD, Linton DM, Forder AA, Plumb H. Imipenem/cilastatin in the treatment of severe nosocomial pneumonia. S Afr Med J. 1988 Oct 15;74(8):390–392. [PubMed]
  • Rapp RP, Billeter M, Hatton J, Young AB, Tibbs PA, Dempsey RJ. Intravenous ciprofloxacin versus ceftazidime for treatment of nosocomial pneumonia and urinary tract infection. Clin Pharm. 1991 Jan;10(1):49–55. [PubMed]
  • Rapp RP, Young B, Bertch K, Tibbs P, Foster TS. Clinical outcome of nosocomial pneumonia following imipenem/cilastatin therapy. Drug Intell Clin Pharm. 1987 Mar;21(3):272–276. [PubMed]
  • Richard C, Pezzano M, Bouhaja B, Rottman E, Rimailho A, Riou B, Auzepy P. Comparison of non-protected lower respiratory tract secretions and protected specimen brush samples in the diagnosis of pneumonia. Intensive Care Med. 1988;14(1):30–33. [PubMed]
  • Rivera-Vazquez CR, Ramirez-Ronda CH, Rodriguez JR, Saavedra S. A comparative analysis of aztreonam + clindamycin versus tobramycin + clindamycin or amikacin + mezlocillin in the treatment of gram-negative lower respiratory tract infections. Chemotherapy. 1989;35 (Suppl 1):89–100. [PubMed]
  • Salata RA, Gebhart RL, Palmer DL, Wade BH, Scheld WM, Groschel DH, Wenzel RP, Mandell GL, Duma RJ. Pneumonia treated with imipenem/cilastatin. Am J Med. 1985 Jun 7;78(6A):104–109. [PubMed]
  • Torres A, Puig de la Bellacasa J, Rodriguez-Roisin R, Jimenez de Anta MT, Agusti-Vidal A. Diagnostic value of telescoping plugged catheters in mechanically ventilated patients with bacterial pneumonia using the Metras catheter. Am Rev Respir Dis. 1988 Jul;138(1):117–120. [PubMed]
  • Torres A, Puig de la Bellacasa J, Xaubet A, Gonzalez J, Rodríguez-Roisin R, Jiménez de Anta MT, Agustí Vidal A. Diagnostic value of quantitative cultures of bronchoalveolar lavage and telescoping plugged catheters in mechanically ventilated patients with bacterial pneumonia. Am Rev Respir Dis. 1989 Aug;140(2):306–310. [PubMed]
  • Torres A, Serra-Batlles J, Ferrer A, Jiménez P, Celis R, Cobo E, Rodriguez-Roisin R. Severe community-acquired pneumonia. Epidemiology and prognostic factors. Am Rev Respir Dis. 1991 Aug;144(2):312–318. [PubMed]
  • Trenholme GM, Pottage JC, Jr, Karakusis PH. Use of ceftazidime in the treatment of nosocomial lower respiratory infections. Am J Med. 1985 Aug 9;79(2A):32–36. [PubMed]
  • Trenholme GM, Schmitt BA, Spear J, Gvazdinskas LC, Levin S. Randomized study of intravenous/oral ciprofloxacin versus ceftazidime in the treatment of hospital and nursing home patients with lower respiratory tract infections. Am J Med. 1989 Nov 30;87(5A):116S–118S. [PubMed]
  • Van Caekenberghe DL, Pattyn SR. In vitro activity of ciprofloxacin compared with those of other new fluorinated piperazinyl-substituted quinoline derivatives. Antimicrob Agents Chemother. 1984 Apr;25(4):518–521. [PMC free article] [PubMed]
  • Wolfson JS, Hooper DC. Fluoroquinolone antimicrobial agents. Clin Microbiol Rev. 1989 Oct;2(4):378–424. [PMC free article] [PubMed]
  • Wunderink RG, Woldenberg LS, Zeiss J, Day CM, Ciemins J, Lacher DA. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia. Chest. 1992 Feb;101(2):458–463. [PubMed]

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