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JAC Advance Access published online on October 29, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg463
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation

John Philpott-Howard 1 , Andrew Burroughs 2 , Neil Fisher 3 , Mark Hastings 4 , Christopher Kibbler 5 , David Mutimer 3 , David Patch 2 , Nancy Rolando 2 , Jim Wade 6 , Julia Wendon 7 , and John O’Grady 7

1 Department of Infectious Diseases, Guy’s, King’s & St Thomas’ School of Medicine, Bessemer Road, London SE5 9PJ;
2 Liver Transplantation and Hepatobiliary Medicine, Royal Free Hospital, Hampstead, London NW3 2QG;
3 Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH;
4 Department of Microbiology, Queen Elizabeth Hospital, Birmingham B15 2TH;
5 Department of Medical Microbiology, Royal Free and University College Medical School, Pond Street, London NW3 2QG;
6 Health Protection Agency London
7 Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK

Received 23 July 2002 ; revised 17 July 2003 ; accepted 1 September 2003

Abstract

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P = 0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P = 0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P = 0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P = 0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.

Keywords: liver transplant, antibiotic therapy, randomized controlled trial, infection
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