Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

A Randomized, Double-blind Clinical Trial Comparing Cefepime Plus Metronidazole With Imipenem-Cilastatin in the Treatment of Complicated Intra-abdominal Infections

A Randomized, Double-blind Clinical Trial Comparing Cefepime Plus Metronidazole With... Abstract Objective: To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients. Design: Prospective, randomized, double-blind multicenter study. Setting: University-affiliated hospitals in the United States and Canada. Patients: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. Intervention: Cefepime, 2 g, was administered intravenously every 12 hours (n=164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen—cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. Main Outcome Assessments: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever. Results: Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenemcilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenemcilastatin—treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%). Conclusion: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.Arch Surg. 1997;132:1294-1302 References 1. Mosdell DM, Morris DM, Voltura A, et al. Antibiotic treatment for surgical peritonitis . Ann Surg . 1991:214:543-549.Crossref 2. Bane PS, Christou NV, Dellinger EP, et al. Pathogenicity of the enterococcus in surgical infections . Ann Surg . 1990:212:155-159.Crossref 3. Barie PS. Emerging problems in gram-positive infections in the postoperative patient . Surg Gynecol Obstet . 1993;177( (suppl) ):S55-S64. 4. Burnett RJ, Haverstock DC, Dellinger EP, et al. Definition of the role of enterococcus in intra-abdominal infection . Surgery . 1995;118:716-721.Crossref 5. Solomkin JS, Dellinger EP, Christou NV, et al. Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections . Ann Surg . 1990;212:581-591.Crossref 6. Buckley MM, Brogden RN, Barradell LB, et al. Imipenem/cilastatin: a reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic effect . Drugs . 1992:44:404-408. 7. Solomkin JS, Reinhart HH, Dellinger EP, et al. Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections . Ann Surg . 1996;233:303-315.Crossref 8. Thornsberry C, Yee YC. Comparative activity of eight antimicrobial agents against clinical bacterial isolates from the United States, measured by two methods . Am J Med . 1996;100( (suppl 6A) ):265-385.Crossref 9. Okamoto MP, Chin M, Gill MA, et al. Analysis of cefepime tissue penetration into human appendix . Pharmacotherapy . 1991;11:353-358. 10. Solomkin JS, Hemsell DL, Sweet R, et al. General guidelines for evaluation of new anti-infective drugs for the treatment of intra-abdominal and pelvic infections . Clin Infect Dis . 1992;15( (suppl 1) ):S33-S42.Crossref 11. Knaus WA, Draper EA. Wagner DP, et al. APACHE II . Crit Care Med . 1985;13: 818-829.Crossref 12. Solomkin JS, Hemsell DL, Sweet R, et al. General guidelines for the evaluation of new anti-infective drugs for the treatment of intra-abdominal infections . In: Beam TR, Gibert DN, Kunin CM, eds. European Guidelines for the Clinical Evaluation of Anti-infective Drug Products 1993 . Brussels, Belgium: European Society of Clinical Microbiology and Infectious Disease; 1993. 13. Lohmann C, Whitman DM, Watch A. and the Peritonitis Study Group. Prospective evaluation of prognostic scoring systems in peritonitis . Eur J Surg . 1993; 159:267-274. 14. Levison MA, Ziegler D. Correlation of APACHE II score, drainage technique, and outcome in postoperative intra-abdominal abscess . Surg Gynecol Obstet . 1991: 172:89-94. 15. Schein M, Gecelter G, Freinkel Z, Gerding H. APACHE II in emergency operation for perforated ulcers . Am J Surg . 1990;159:309-313.Crossref 16. Barie PS, Hydo LJ, Fischer E. Predictive value of APACHE severity scoring for the development of multiple organ dysfunction syndrome in critically ill patients with perforated viscus . Arch Surg . 1996;131:37-43.Crossref 17. Bohnen JM, Mustard RA. Oxholm SE, Schouten BD. APACHE II score and abdominal sepsis: a prospective study . Arch Surg . 1988;123:225-229.Crossref 18. Barie PS, Hydo L, Fischer E. Comparison of APACHE II and III scoring systems for mortality prediction in critical surgical illness . Arch Surg . 1995;130:77-82.Crossref 19. Christou NV. Barie PS, Dellinger EP, et al. Surgical Infection Society Intra-abdominal Infection Study . Arch Surg . 1993;128:193-199.Crossref 20. Weigelt JA, Easley SM, Thal ER, et al. Abdominal surgical wound infection is lowered with improved perioperative Enterococcus and Bacteroides therapy . J Trauma . 1993;34:579-584.Crossref 21. Christou NV, Turgeon P, Wassef R, et al. Management of intra-abdominal infections . Arch Surg . 1996;131:1193-1201.Crossref 22. Brismar B, Malmborg AS, Tunevall G, et al. Piperacillin-tazobactam versus imipenem-cilastatin for treatment of intra-abdominal infections . Antimicrob Agents Chemother . 1992;36:2766-2773.Crossref 23. Wise R, Donovan IA, Lockley MR, et al. The pharmacokinetics and tissue penetration of imipenem . J Antimicrob Chemother . 1986;18( (suppl E) ):93-101.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

A Randomized, Double-blind Clinical Trial Comparing Cefepime Plus Metronidazole With Imipenem-Cilastatin in the Treatment of Complicated Intra-abdominal Infections

Loading next page...
 
/lp/american-medical-association/a-randomized-double-blind-clinical-trial-comparing-cefepime-plus-SUAZf6SZYJ

References (30)

Publisher
American Medical Association
Copyright
Copyright © 1997 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1997.01430360040008
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective: To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients. Design: Prospective, randomized, double-blind multicenter study. Setting: University-affiliated hospitals in the United States and Canada. Patients: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. Intervention: Cefepime, 2 g, was administered intravenously every 12 hours (n=164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen—cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. Main Outcome Assessments: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever. Results: Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenemcilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenemcilastatin—treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%). Conclusion: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.Arch Surg. 1997;132:1294-1302 References 1. Mosdell DM, Morris DM, Voltura A, et al. Antibiotic treatment for surgical peritonitis . Ann Surg . 1991:214:543-549.Crossref 2. Bane PS, Christou NV, Dellinger EP, et al. Pathogenicity of the enterococcus in surgical infections . Ann Surg . 1990:212:155-159.Crossref 3. Barie PS. Emerging problems in gram-positive infections in the postoperative patient . Surg Gynecol Obstet . 1993;177( (suppl) ):S55-S64. 4. Burnett RJ, Haverstock DC, Dellinger EP, et al. Definition of the role of enterococcus in intra-abdominal infection . Surgery . 1995;118:716-721.Crossref 5. Solomkin JS, Dellinger EP, Christou NV, et al. Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections . Ann Surg . 1990;212:581-591.Crossref 6. Buckley MM, Brogden RN, Barradell LB, et al. Imipenem/cilastatin: a reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic effect . Drugs . 1992:44:404-408. 7. Solomkin JS, Reinhart HH, Dellinger EP, et al. Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections . Ann Surg . 1996;233:303-315.Crossref 8. Thornsberry C, Yee YC. Comparative activity of eight antimicrobial agents against clinical bacterial isolates from the United States, measured by two methods . Am J Med . 1996;100( (suppl 6A) ):265-385.Crossref 9. Okamoto MP, Chin M, Gill MA, et al. Analysis of cefepime tissue penetration into human appendix . Pharmacotherapy . 1991;11:353-358. 10. Solomkin JS, Hemsell DL, Sweet R, et al. General guidelines for evaluation of new anti-infective drugs for the treatment of intra-abdominal and pelvic infections . Clin Infect Dis . 1992;15( (suppl 1) ):S33-S42.Crossref 11. Knaus WA, Draper EA. Wagner DP, et al. APACHE II . Crit Care Med . 1985;13: 818-829.Crossref 12. Solomkin JS, Hemsell DL, Sweet R, et al. General guidelines for the evaluation of new anti-infective drugs for the treatment of intra-abdominal infections . In: Beam TR, Gibert DN, Kunin CM, eds. European Guidelines for the Clinical Evaluation of Anti-infective Drug Products 1993 . Brussels, Belgium: European Society of Clinical Microbiology and Infectious Disease; 1993. 13. Lohmann C, Whitman DM, Watch A. and the Peritonitis Study Group. Prospective evaluation of prognostic scoring systems in peritonitis . Eur J Surg . 1993; 159:267-274. 14. Levison MA, Ziegler D. Correlation of APACHE II score, drainage technique, and outcome in postoperative intra-abdominal abscess . Surg Gynecol Obstet . 1991: 172:89-94. 15. Schein M, Gecelter G, Freinkel Z, Gerding H. APACHE II in emergency operation for perforated ulcers . Am J Surg . 1990;159:309-313.Crossref 16. Barie PS, Hydo LJ, Fischer E. Predictive value of APACHE severity scoring for the development of multiple organ dysfunction syndrome in critically ill patients with perforated viscus . Arch Surg . 1996;131:37-43.Crossref 17. Bohnen JM, Mustard RA. Oxholm SE, Schouten BD. APACHE II score and abdominal sepsis: a prospective study . Arch Surg . 1988;123:225-229.Crossref 18. Barie PS, Hydo L, Fischer E. Comparison of APACHE II and III scoring systems for mortality prediction in critical surgical illness . Arch Surg . 1995;130:77-82.Crossref 19. Christou NV. Barie PS, Dellinger EP, et al. Surgical Infection Society Intra-abdominal Infection Study . Arch Surg . 1993;128:193-199.Crossref 20. Weigelt JA, Easley SM, Thal ER, et al. Abdominal surgical wound infection is lowered with improved perioperative Enterococcus and Bacteroides therapy . J Trauma . 1993;34:579-584.Crossref 21. Christou NV, Turgeon P, Wassef R, et al. Management of intra-abdominal infections . Arch Surg . 1996;131:1193-1201.Crossref 22. Brismar B, Malmborg AS, Tunevall G, et al. Piperacillin-tazobactam versus imipenem-cilastatin for treatment of intra-abdominal infections . Antimicrob Agents Chemother . 1992;36:2766-2773.Crossref 23. Wise R, Donovan IA, Lockley MR, et al. The pharmacokinetics and tissue penetration of imipenem . J Antimicrob Chemother . 1986;18( (suppl E) ):93-101.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Dec 1, 1997

There are no references for this article.