Cost high. acceptable. worst. best. acceptable. Cost low

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Key words I

Effect low worst acceptable Cost high Cost low acceptable best Effect high Fig. 1. Cost-Effectiveness. The best case is low cost and high efficacy. The acceptable cases are low cost and efficacy as well as high cost and efficacy. The worst case is high cost and low efficacy. II III

IV V

Ref Type of Evaluation 13 Cost-minimization 14 Cost-minimization 15 Cost-benefit 16 Cost-benefit 17 Cost-effectiveness, cost-benefit 18 Cost-effectiveness, cost-benefit No. Interventions or Patients 225 patients 238 interventions 199,082 patients 16,860 interventions 102 patients 7,219 patients Table 1. Economic effect of drug intervention by the clinical pharmacist in Study Setting (Country) Tertiary care teaching Community 961 s Community 2 tertiary care teaching s Teaching Study Period (Cost Year) 3 mo (1997) 18 mo (1999) 1 yr (1996) 18 mo (1998) 172 days (1994) 2 periods of 2 yr (1996) Pharmacist s Intervention(s) Reviewed medical records to optimize antibiotic therapy Outcome(s) Savings of $386.80 per patient based on charges, extrapolated to savings of $390,000/yr; lesser use of antibiotics expressed as diminution of 3.43 defined daily doses of i.v. antibiotics and 1.41 days of antibiotic therapy Optimized Differences of antibiotic therapy $4,404/intervention in median patient charges and $2,642/ intervention in median patient costs; cost of personnel estimated at $21,000/yr Managed vancomycin and amino- total charges, 8% on Savings of 6% on glycoside therapy drug charges, and 8% on laboratory charges; decreases of 7% in death rate and 12% in LOS Substituted antibiotics in the treatment of CAP Reviewed antibiotic therapy for switching i.v. drugs to oral drugs Reviewed prescriptions for restricted or nonformulary i.v. antimicrobials Savings of $22,316/ yr; decrease of 1.2 days in LOS; lower readmission rate (2.4% vs. 3.4%) Estimated savings of $5,800/yr; costs of operating such a program estimated at $22,200/yr Savings of $291,885. Decline of 31% in i.v. antimicrobial costs, extrapolated to savings of $145,942/ yr; mean decreases of 2.4 days in LOS and 1.67% in mortality Study Type Prospective, randomized controlled trial Prospective, randomized clinical trial Multicenter, retrospective cohort study Outcomes Evaluated Cost Other Antibiotics Clinical and microbial outcome Antibiotics, LOS laboratory, medications, room and board Drugs, laboratory monitoring Death rate, LOS, no. complications Measurement and Valuation of Outcomes Charges for antibiotic therapy Charges derived from patient billing; conversion to cost by multiplying patient charges by estimated factor of 0.60 Costs calculated using charges for drugs and laboratories Prospective Direct cost LOS, Costs of cohort study of use of readmission antibiotic antibiotics probability and overall cost therapy calculated using drug acquisition cost Prospective, randomized clinical trial Retrospective beforeafter study Antibiotics LOS, Difference in cost between mortality, antibiotic 30-day therapy before readmission, need intervention; and after to restart i.v. origin of cost therapy not specified Antibiotics LOS, Acquisition mortality, cost per period readmission β

Table 2. Basic characteristics Intervention group Non-intervention group P value Number of patients 33 30 Age (years) (mean SD) 76.8 13.0 79.0 10.6 0.464 Gender (male : female) 17 : 16 13 : 17 Ccr (ml/min) (mean SD) 44.8 28.1 37.0 19.6 0.201 CRP (mg/dl) (mean SD) 14.9 7.2 15.5 8.9 0.775 Body temperature ( ) (mean SD) 38.5 1.0 38.3 0.9 0.866 Pulse rate (time/min) (mean SD) 104.7 18.4 100.0 14.6 0.275 Respiratory rate (time/min) (mean SD) 21.2 2.2 20.4 3.1 0.327 WBC ( 10 3 / L) (mean SD) 17,009.1 10,414.1 16,226.7 7,229.3 0.731 SIRS SCORE 3.2 0.8 2.9 0.8 0.282 Underlying disease (main factor) Diabetes mellitus 6 (18.1%) 7 (23.3%) 0.613 Renal dysfunction 5 (15.2%) 3 (10.0%) 0.545 Liver dysfunction 3 (9.1%) 5 (16.7%) 0.376 Immunosuppression 5 (15.2%) 4 (13.3%) 0.832 Urinary tract obstruction 14 (42.4%) 11 (36.7%) 0.641 Pathogen in blood and urine Escherichia coli 17 (51.5%) 21 (70.0%) 0.134 Klebsiella pneumoniae 7 (21.3%) 3 (10.0%) 0.224 Pseudomonas aeruginosa 4 (12.1%) 4 (13.4%) 0.863 Enterobacter species 3 (9.1%) 0 (0%) 0.095 Proteus mirabilis 1 (3.0%) 1 (3.3%) 0.951 Serratia marcescens 1 (3.0%) 1 (3.3%) 0.951 Initial treatment drug TAZ/PIPC 10 (30.3%) 8 (26.7%) 0.755 4 th generation Cephems 4 (12.1%) 3 (10.0%) 0.791 Carbapenems 19 (57.6%) 18 (60.0%) 0.859 Quinolone 0 (0%) 1 (3.3%) 0.293 At the time of a septicemic diagnosis Ccr was calculated using the Cockcroft-Gault formula. Renal dysfunction was defined as less than Ccr 50 ml/min. Liver dysfunction was defined as liver cirrhosis, liver cancer. χ

Table 3. Results of pharmacist intervention for septicemic patients Intervention group (n 33) Suggestion of de-escalation 1 Penicillin 2 (6.1%) 1 st generation Cephem 7 (21.2%) 2 nd generation Cephems 16 (48.4%) 3 rd generation Cephem 2 4 (12.1%) Aminoglycosides 2 (6.1%) Suggestion of dose adjustment for renal dysfunction 2 (6.1%) 1 Antimicrobial agents were changed after the identification of any pathogen in blood culture. 2 When the only pathogen detected was Pseudomonas aeruginosa, we suggested the use of a 3 rd generation Cephem. Penicillin was ampicillin. 1 st generation Cephem was cefazolin. 2 nd generation Cephems were cefotiam, cefmetazole. 3 rd generation Cephem was ceftazidime. Aminoglycosides were gentamicin and amikacin. Table 4. Result of the cost and effect study Intervention group (n 33) Non-intervention group (n 30) P value The antimicrobial cost amounts in the average daily per capita (yen) (mean SD) 2,589 1,318 3,702 2,024 0.011 The average total antimicrobial cost amount per capita (yen) (mean SD) 31,625 19,272 49,360 25,960 0.002 The average number of days until healing (days) (mean SD) 1 14.9 5.0 14.2 4.1 0.744 The average duration of ization due to sepsis (days) (mean SD) 2 19.6 7.7 22.8 10.1 0.221 1 two one sided test: P 0.000 2 two one sided test: P 0.011 Table 5.Comparison of the antimicrobial cost amount per capita before and after pharmacist intervention Average daily antimicrobial cost amount per capita (yen) (mean SD) Before After P value 4,104 2,022 1,202 906 0.000

Table 6. Basic characteristics Intervention group Non-intervention group P value Number of patients 19 19 Age (year) (mean SD) 69.4 20.8 77.5 13.8 0.171 Gender (male : female) 12 : 7 9 : 10 CCr (ml/min) (mean SD) 65.2 17.3 54.6 21.3 0.102 CRP (mg/dl) (mean SD) 13.3 7.2 14.4 7.5 0.675 BUN (mg/dl) (mean SD) 16.3 8.6 26.9 24.0 0.081 Body temperature ( ) (mean SD) 38.0 0.7 37.9 0.8 0.791 SpO2 (%) (mean SD) 94.4 2.3 91.4 4.2 0.015 WBC ( 10 3 / L) (mean SD) 11,652.6 3,564.1 13,700.0 5,383.7 0.181 Systolic blood pressure (mmhg) (mean SD) 115.9 19.8 115.4 18.7 0.931 A-DROP score 1.4 0.7 1.7 0.7 0.272 Initial treatment drug (intravenous injection) Penicillins 9 (47.3%) 12 (63.2%) 0.334 Cephems 6 (31.5%) 7 (36.8%) 0.738 Carbapenem 1 (5.3%) 0 (0%) 0.310 Tetracycline 1 (5.3%) 0 (0%) 0.310 Quinolone 1 (5.3%) 0 (0%) 0.310 Lincomycin 1 (5.3%) 0 (0%) 0.310 Table 7.Result of pharmacist intervention for community-acquired pneumonia patients with S. pneumoniae Suggestion of oral switch (after patient was getting better) Intervention group (n 19) Penicillins 8 (42.1%) Cephems 4 (21.1%) Quinolones 4 (21.1%) Macrolide 2 (10.5%) Tetracycline 1 (5.2%) Penicillins were amoxicillin, ampicillin. Cephems were cefaclor, cefditoren pivoxil, cefcapene pivoxil. Quinolones were ciprofloxacin, levofloxacin. Macrolide was clarithromycin. Tetracycline was minocycline. Streptococcus pneumoniae χ

Table 8. Result of the cost and effect study Intervention group (n 33) Non-intervention group (n 30) P value The average total antimicrobial cost amount per capita (yen) (mean SD) 16,125 7,696 25,455 16,860 0.038 The average ization cost (yen) (mean SD) 340,287 100,485 435,604 108,476 0.009 The average number of days administration injection drug (days) (mean SD) 5.4 1.6 9.1 3.1 0.001 The average duration of ization (days) (mean SD) 9.1 3.8 11.6 2.9 0.030 VI