title: Accounting for the development of antibacterial resistance in the cost effectiveness of ertapenem versus piperacillin/tazobactam in the treatment of diabetic foot infections in the UK.
abstract: OBJECTIVE
  Increased antibacterial use is associated with a greater likelihood of reduced effectiveness as a result of resistance development in the future. The objective of this study was to evaluate the cost effectiveness of ertapenem versus piperacillin/tazobactam in the treatment of diabetic foot infections (DFIs) from the UK NHS perspective, accounting for the development of antibacterial resistance over time.
  
  
  METHODS
  A decision-tree model was developed to estimate the cost effectiveness of ertapenem versus piperacillin/tazobactam at different timepoints in the 36 months following introduction of treatment. Development of antibacterial resistance was incorporated in the analysis using a previously published compartment (susceptible-infected-susceptible) model. The development of resistance was a function of the clearance rate of pathogens and the size of the proportion of the population prescribed the antibacterial. The microbiological clearance rate and clinical success rates were assumed to be related and were obtained from the SIDESTEP study. These data included resistant pathogens (either acquired or intrinsic resistance) such as Enterobacteriaceae, meticillin-resistant Staphylococcus aureus, enterococci and Pseudomonas aeruginosa. Model outcomes over time included lifetime QALYs, direct medical costs (year 2006 values) and cost per QALY saved. Clinical efficacy of second-line treatment, direct medical costs and utilities were derived from other existing studies. Probabilistic sensitivity analyses were undertaken to estimate the uncertainty of model outcomes. Costs and QALYs were discounted at 3.5% per annum.
  
  
  RESULTS
  The model suggested savings of pound407 (95% uncertainty interval [UI] -337, 1501) per patient when DFIs were treated with ertapenem instead of piperacillin/tazobactam after 1 month's treatment. Probabilistic sensitivity analysis suggested a 91% probability of the incremental cost per QALY saved being within a threshold for cost effectiveness of pound20,000. After 3 years it is expected that the antibacterial resistance profile with piperacillin/tazobactam would increase at a greater rate than with ertapenem. As a result, the cost savings with ertapenem are expected to increase to pound3465 (95% UI 2502, 4564), and ertapenem will additionally result in greater clinical success rates and lifetime QALY savings (1.16; 95% UI 0.46, 2.06).
  
  
  CONCLUSIONS
  Ertapenem appears to be a cost-saving and possibly an economically dominant therapy over piperacillin/tazobactam for the treatment of patients with DFIs from the UK NHS perspective.
authors.affiliation: Mapi Values, Boston, Massachusetts 02114, USA. Jeroen.jansen@mapivalues.com
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: Jansen
authors.forename: Ritesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D017719:Diabetic Foot / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D004180:Direct Service Costs; D016527:Drug Costs; D024881:Drug Resistance, Bacterial; D000077727:Ertapenem; D006801:Humans; D008954:Models, Biological; D017059:Models, Econometric; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D019057:Quality-Adjusted Life Years; D016896:Treatment Outcome; D006113:United Kingdom; D047090:beta-Lactams / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077727:Ertapenem; D010878:Piperacillin