Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.
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.
Department of Infectious Diseases, Guy's, King's & St Thomas' School of Medicine, Bessemer Road, London SE5 9PJ, UK. john.philpott-howard@kcl.ac.uk
John
J
Philpott-Howard
Andrew
A
Burroughs
Neil
N
Fisher
Mark
M
Hastings
Christopher
C
Kibbler
David
D
Mutimer
David
D
Patch
Nancy
N
Rolando
Jim
J
Wade
Julia
J
Wendon
John
J
O'Grady
D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D002939:Ciprofloxacin / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000187:drug effects; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D010397:Penicillanic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D010406:Penicillins / Q000009:adverse effects / Q000627:therapeutic use*; D010878:Piperacillin / Q000009:adverse effects / Q000627:therapeutic use*; D000077725:Piperacillin, Tazobactam Drug Combination; D011183:Postoperative Complications / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D010406:Penicillins; D008795:Metronidazole; D000077725:Piperacillin, Tazobactam Drug Combination; D002939:Ciprofloxacin; D000658:Amoxicillin; D010397:Penicillanic Acid; D010878:Piperacillin