Cost-effectiveness of selective digestive decontamination (SDD) versus selective oropharyngeal decontamination (SOD) in intensive care units with low levels of antimicrobial resistance: an individual patient data meta-analysis.

OBJECTIVE: To determine the cost-effectiveness of selective digestive decontamination (SDD) as compared to selective oropharyngeal decontamination (SOD) in intensive care units (ICUs) with low levels of antimicrobial resistance. DESIGN: Post-hoc analysis of a previously performed individual patient data meta-analysis of two cluster-randomised cross-over trials. SETTING: 24 ICUs in the Netherlands. PARTICIPANTS: 12 952 ICU patients who were treated with ≥1 dose of SDD (n=6720) or SOD (n=6232). INTERVENTIONS: SDD versus SOD. PRIMARY AND SECONDARY OUTCOME MEASURES: The incremental cost-effectiveness ratio (ICER; ie, costs to prevent one in-hospital death) was calculated by comparing differences in direct healthcare costs and in-hospital mortality of patients treated with SDD versus SOD. A willingness-to-pay curve was plotted to reflect the probability of cost-effectiveness of SDD for a range of different values of maximum costs per prevented in-hospital death. RESULTS: The ICER resulting from the fixed-effect meta-analysis, adjusted for clustering and differences in baseline characteristics, showed that SDD significantly reduced in-hospital mortality (adjusted absolute risk reduction 0.0195, 95% CI 0.0050 to 0.0338) with no difference in costs (adjusted cost difference €62 in favour of SDD, 95% CI -€1079 to €935). Thus, SDD yielded significantly lower in-hospital mortality and comparable costs as compared with SOD. At a willingness-to-pay value of €33 633 per one prevented in-hospital death, SDD had a probability of 90.0% to be cost-effective as compared with SOD. CONCLUSION: In Dutch ICUs, SDD has a very high probability of cost-effectiveness as compared to SOD. These data support the implementation of SDD in settings with low levels of antimicrobial resistance.

Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs. OBJECTIVES: Inhaled tobramycin, used to manage P. aeruginosa infection in CF patients, is available as powder (tobramycin inhalation powder, TIP) and solution (tobramycin inhalation solution, TIS). Evidence suggests increased adherence with the use of TIP over TIS. Hence, this analysis aimed to evaluate the potential pharmacoeconomic benefit of increased adherence with TIP over TIS in the US setting. METHODS: A patient-level simulation model was developed to compare TIP with TIS. Both costs and benefits were predicted over a 10-year time horizon from a payer's perspective, and were discounted annually at 3%. All costs were presented in 2016 US dollars. RESULTS: TIP was associated with greater quality-adjusted life-years (by 0.27) and lower total costs (by US$36,168) as compared with TIS over a 10-year time horizon. TIP-treated patients experienced a decreased mean number of exacerbations than TIS-treated patients (39.24 vs 50.20). Furthermore, administration of TIP via the T-326 Inhaler was associated with significant cost savings per patient, because of the nebulizer required for administering TIS (by US$1596) and exacerbation costs (by US$76,531). Probabilistic sensitivity analysis showed that TIP was dominant over TIS in 100% of the simulations. CONCLUSION: TIP is likely to be a more cost-effective treatment than TIS, and therefore may reduce the economic burden of CF.

Inhaled aztreonam lysine versus inhaled tobramycin in cystic fibrosis. An economic evaluation.

RATIONALE: Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients with cystic fibrosis and is associated with a high economic burden. A recently published comparator trial demonstrated that outcomes in patients with cystic fibrosis with chronic P. aeruginosa infections switched from tobramycin solution for inhalation to aztreonam lysine for inhalation were better than those of patients who continued on tobramycin. OBJECTIVES: To compare overall costs of treatment of chronic inhaled tobramycin and aztreonam lysine in patient with cystic fibrosis who have chronic Pseudomonas infection, taking differences in outcomes into account. METHODS: A cost-effectiveness analysis with a 3-year time horizon was performed to simulate the economic consequences of either treatment from the perspective of a third party payer in the United States. We extrapolated results from the comparator trial and used data regarding clinical outcomes, quality of life, and costs from published literature and proprietary databases. A Markov structure was used to consider transitions between health states, defined principally by levels of percent predicted of FEV1. Extensive scenario and probabilistic sensitivity analyses were performed. MEASUREMENTS AND MAIN RESULTS: Use of aztreonam lysine for inhalation was associated with an average cost saving of $41,947 per patient over 3 years, as well as greater quality-adjusted life-years and total life-years. Scenario analyses demonstrated that these findings were robust to changes in key assumptions. CONCLUSIONS: It appears, with high likelihood, that the use of aztreonam solution for inhalation is associated with cost savings, an increase in quality-adjusted life-years, and improved clinical outcomes among patients with extensive prior use of tobramycin solution for inhalation who are naive to inhaled aztreonam lysine.

The economics of using prophylactic antibiotic-loaded bone cement in total knee replacement.

The rate of peri-prosthetic infection following total joint replacement continues to rise, and attempts to curb this trend have included the use of antibiotic-loaded bone cement at the time of primary surgery. We have investigated the clinical- and cost-effectiveness of the use of antibiotic-loaded cement for primary total knee replacement (TKR) by comparing the rate of infection in 3048 TKRs performed without loaded cement over a three-year period versus the incidence of infection after 4830 TKRs performed with tobramycin-loaded cement over a later period of time of a similar duration. In order to adjust for confounding factors, the rate of infection in 3347 and 4702 uncemented total hip replacements (THR) performed during the same time periods, respectively, was also examined. There were no significant differences in the characteristics of the patients in the different cohorts. The absolute rate of infection increased when antibiotic-loaded cement was used in TKR. However, this rate of increase was less than the rate of increase in infection following uncemented THR during the same period. If the rise in the rate of infection observed in THR were extrapolated to the TKR cohort, 18 additional cases of infection would have been expected to occur in the cohort receiving antibiotic-loaded cement, compared with the number observed. Depending on the type of antibiotic-loaded cement that is used, its cost in all primary TKRs ranges between USD $2112.72 and USD $112 606.67 per case of infection that is prevented.

The cost effectiveness of dry powder antibiotics for the treatment of Pseudomonas aeruginosa in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) affects over 9,000 people in the UK and limits life expectancy. CF patients are susceptible to lung infections, most commonly Pseudomonas aeruginosa. Once infection is established, patients require lifetime treatment using nebulised antibiotics. Newer dry powder formulations of antibiotics may reduce treatment burden and improve compliance. OBJECTIVE: Our objective was to evaluate the cost effectiveness of (i) colistimethate sodium dry powder for inhalation (DPI) and (ii) tobramycin DPI versus nebulised tobramycin for the treatment of chronic P. aeruginosa lung infection in patients with CF from the perspective of the National Health Service (NHS) and Personal Social Services (PSS). METHODS: We developed a state transition model based on transitions between three strata of lung function measured in terms of forced expiratory volume in 1 second (FEV1) % predicted. Additional health states representing post-lung transplantation and dead are also modelled. The model structure was informed by systematic reviews of evidence concerning the plausibility of potential relationships between intermediate endpoints and final outcomes. The model assumes that treatment impacts on FEV1 trajectory, which manifest as changes in health-related quality of life. No survival benefit is assumed due to the absence of robust quantifiable evidence. Model parameters were informed by patient-level and aggregate data from two randomised controlled trials together with the best available evidence from the literature. Resource use and costs associated with drug acquisition, the management of exacerbations and reduced nebuliser maintenance were drawn from reference sources and expert opinion. Costs were valued at 2011/2012 prices. Costs and health outcomes were discounted at a rate of 3.5 %. Simple and probabilistic sensitivity analyses were undertaken, including additional analyses of Patient Access Scheme (PAS) price discounts offered by the manufacturers of both DPI products. RESULTS: Colistimethate sodium DPI is expected to produce fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Based on its list price, colistimethate sodium DPI is expected to be dominated by nebulised tobramycin. When the PAS is incorporated, the incremental cost-effectiveness ratio (ICER) for colistimethate sodium DPI versus nebulised tobramycin is expected to be approximately £288,600 saved per QALY lost. Based on its current list price, the ICER for tobramycin DPI versus nebulised tobramycin is expected to be approximately £124,000 per QALY gained. When the proposed PAS is included, tobramycin DPI is expected to dominate nebulised tobramycin. CONCLUSIONS: Under their list prices, neither DPI product is likely to represent good value for money for the NHS given current cost-effectiveness thresholds. The PAS discounts have a significant impact upon the economic attractiveness of both DPI products compared against nebulised tobramycin. The clinical effectiveness and cost effectiveness of the DPIs against other nebulised antibiotics, such as aztreonam and inhaled colistimethate sodium, remains unclear.

Colistimethate sodium powder and tobramycin powder for inhalation for the treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis: systematic review and economic model.

BACKGROUND: Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of thick sticky mucus in the lungs, pancreas, liver, intestine and reproductive tract, and an increase in the salt content in sweat. Among other problems, people with CF experience recurrent respiratory infections and have difficulties digesting food. CF affects over 9000 individuals in the UK. CF shortens life expectancy and adversely affects quality of life. In 2010, CF was recorded as the cause of 103 deaths in England and Wales. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of colistimethate sodium dry powder for inhalation (DPI) (Colobreathe(®), Forest Laboratories) and tobramycin DPI (TOBI Podhaler(®), Novartis Pharmaceuticals) for the treatment of Pseudomonas aeruginosa lung infection in CF. DATA SOURCES: Electronic databases were searched in February and March 2011 [MEDLINE, MEDLINE In-Process & Other Non-Indexed citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Conference Proceedings Citation Index (CPCI) and Bioscience Information Service (BIOSIS) Previews]. Relevant databases were searched for ongoing and unpublished studies, and bibliographies of relevant systematic reviews and the manufacturers' submissions were also hand-searched. REVIEW METHODS: A systematic review of the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI for the treatment of chronic P. aeruginosa lung infection in CF was conducted. Existing economic evidence within the literature was reviewed and a de novo health economic model was also developed. RESULTS: Three randomised controlled trials (RCTs) were included in the clinical effectiveness review. Both colistimethate sodium DPI and tobramycin DPI were reported to be non-inferior to nebulised tobramycin for the outcome forced expiratory volume in first second percentage predicted (FEV1%). It was not possible to draw any firm conclusions as to the relative efficacy of colistimethate sodium DPI compared with tobramycin DPI. The economic analysis suggests that colistimethate sodium DPI produces fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Given the incremental discounted lifetime cost of tobramycin DPI compared with nebulised tobramycin, it highly unlikely that tobramycin DPI has an incremental cost-effectiveness ratio that is better than £30,000 per QALY gained. LIMITATION: The uncertainty surrounding the short-term evidence base inevitably results in uncertainty surrounding the long-term clinical effectiveness and cost-effectiveness of colistimethate sodium DPI. CONCLUSIONS: Both DPI formulations have been shown to be non-inferior to nebulised tobramycin as measured by FEV1%. The results of these trials should be interpreted with caution owing to the means by which the results were analysed, the length of follow-up, and concerns about the ability of FEV1% to accurately represent changes in lung health. Although the increase in QALYs is expected to be lower with colistimethate sodium DPI than with nebulised tobramycin, a price for this intervention had not been agreed at the time of the assessment. Depending on the price of colistimethate sodium DPI, this results either in a situation whereby colistimethate sodium DPI is dominated by nebulised tobramycin or in one whereby the incremental cost-effectiveness of nebulised tobramycin compared with colistimethate sodium DPI is in the range of £24,000-277,000 per QALY gained. The economic analysis also suggests that, given its price, it is unlikely that tobramycin DPI has a cost-effectiveness ratio of < £30,000 per QALY gained when compared with nebulised tobramycin. A RCT to assess the longer-term (≥ 12 months) efficacy of colistimethate sodium DPI and tobramycin DPI in comparison with nebulised treatments would be beneficial. Such a study should include the direct assessment of HRQoL using a relevant preference-based instrument. Future studies should ensure that the European Medicines Agency guidelines are adhered to. In addition, high-quality research concerning the relationship between forced expiratory volume in first second % (FEV1%) predicted or other measures of lung function and survival/health-related quality of life (HRQoL) would be useful. STUDY REGISTRATION: PROSPERO CRD42011001350. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Economic impact of tobramycin in patients with cystic fibrosis in a managed care population.

OBJECTIVE: Guidelines recommend chronic use of tobramycin solution for inhalation (TSI) for cystic fibrosis (CF) patients with moderate-to-severe lung disease and persistent airway Pseudomonas aeruginosa. This study evaluated the economic impact of TSI in managed care CF patients. METHODS: Patients (0-64 years) with ≥2 CF medical claims between 01/01/04-03/31/09 were identified. For TSI users, the index date was the first TSI claim in the period; for non-users, a pseudo-index date was determined and randomly assigned by simulating the distribution of index dates of TSI users. Maximum sample size was obtained for patients with ≥3 months pre- and ≥12 months post-index eligibility. Users were categorized by number of TSI prescriptions filled during 12-month post-index period as low (1 fill), medium (2-3 fills) and high adherence (≥4 fills). Differences in per member per month (PMPM) costs pre-index to post-index were analyzed using paired t-tests. RESULTS: A total of 388 TSI users (mean age 19 years, 48% female) and 444 non-users (mean age 30 years, 54% female) met study criteria. In users, total and CF-related PMPM costs decreased $959 (17%) and $113 (3%), respectively, after starting TSI. Among TSI users, CF-related inpatient PMPM costs decreased by $1171 (49%; p=0.01), while CF-related prescription PMPM costs increased by $992 (p<0.01). CF-related inpatient PMPM costs decreased by $381 (38%; p=0.16) for low and $1425 (50%; p=0.21) for medium users and decreased by $1829 (51%; p=0.02) for high users. LIMITATIONS: Limitations include use of administrative claims data, small sample size due to disease rarity, random assignment of pseudo-index date to non-users and differences in baseline characteristics between TSI users and non-users. CONCLUSION: All-cause and CF-related PMPM medical costs significantly decreased after TSI initiation. Among TSI users, total healthcare costs decreased, although not significantly, due to PMPM increases in prescription costs. A trend towards greater decrease in inpatient PMPM costs was observed with increasing TSI adherence.

Budget impact model of tobramycin inhalation solution for treatment of Pseudomonas aeruginosa in cystic fibrosis patients.

BACKGROUND: Pseudomonas aeruginosa (PA) is the most common airway pathogen in cystic fibrosis (CF) patients. The objective of this analysis was to determine the costs of managing PA infection in CF patients with a chronic regimen of tobramycin inhalation solution (TIS). METHODS: A budget impact model of CF patients was developed to evaluate the costs of TIS from a US managed-care organization (MCO) perspective. The Microsoft Excel model compared TIS treatment plus standard care with standard care alone over a 4-year time horizon and included the cost of drugs, medical care, and annual probabilities of hospitalization and IV anti-pseudomonal (anti-PA) antibiotics administration. RESULTS: For an MCO with 5,000,000 members, 389 members 6 years of age or older were estimated to have CF, and 218 (56%) had PA infection. Assuming that use of TIS increased from 20% to 25%, the 1-year budget increased $231,251 or from $0.049 to $0.053 per member per month (PMPM). The net drug budget increase was $243,919, while medical costs associated with exacerbation management decreased $12,669 over the first year. Increasing utilization of TIS, from 20% to 40% over 4 years resulted in an incremental overall budget increase of $925,002, a 3% decrease in hospitalizations, and a 4% decrease in administrations of IV anti-PA antibiotics. These reductions translated to a medical care cost saving of $50,676 over 4 years. Limitations of this study include that the clinical data for the model are from clinical trials conducted in 1996 and the estimation of TIS use for CF patients with chronic PA infections can be impacted by TIS adherence. CONCLUSION: Model results suggest that increasing the use of TIS decreases medical care costs due to decreased hospital admissions and the use of IV anti-PA antibiotics at the expense of higher drug costs.

The costs of treatment of early and chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

Costs, quality of life and treatment compliance associated with antibiotic therapies in patients with cystic fibrosis: a review of the literature.

BACKGROUND: Cystic fibrosis is the most common incurable hereditary disease in the US. Persistent respiratory infection is the leading cause of morbidity and mortality in cystic fibrosis patients. OBJECTIVE: This study aimed to review the literature on economic and quality of life outcomes and treatment compliance associated with antibiotic therapies for cystic fibrosis patients. METHODS: A systematic literature review was conducted using keyword searches of the MEDLINE database and selected conference abstracts. The review covered studies published between January 1990 and May 2007. RESULTS/CONCLUSIONS: Evidence suggests that inhaled tobramycin, a key chronic suppressive therapy, can reduce other healthcare costs. The main determinants of the cost of care include disease severity and respiratory infection. Costs vary widely by country. There is evidence that inhaled tobramycin and oral azithromycin improve quality of life and that treatment setting and patient convenience may also impact on quality of life. Antibiotic treatment compliance varied significantly and depended on the method of measurement, with more subjective measures tending to be higher. This review concludes by offering directions for future research.

Economic evaluation of Tobramycin nebuliser solution in cystic fibrosis.

BACKGROUND: The cost effectiveness of inhaled TOBIR tobramycin nebuliser solution (TNS) in CF and chronic pulmonary Pseudomonas aeruginosa infection has been shown in US but not in European studies. METHODS: An economic evaluation of TNS was undertaken in children and adults. Lung function and resource utilisation were recorded for 24 months before and during TNS therapy. Interventions were costed. RESULTS: Forty-one patients received TNS; 30 of them matched with a paired control on usual therapy. TNS cases received more inhaled and IV antibiotics in the year before TNS than controls, and were hospitalised more. In the TNS treated group mean days in hospital before and after (change) were 32.0, 24.2 (-7.8); days on IV antibiotics 55.4, 38.9 (-16.4); total cost 22,102 pounds, 28,394 pounds (+ 6292 pounds), composed of cost of TNS 0 pounds, 10,010 pounds (+ 10,010 pounds), cost of hospitalisation 10,897 pounds, 8552 pounds (- 2345 pounds), cost of drugs 11,205 pounds, 9832 pounds (- 1374 pounds). In 19 patients aged < 18 the change in days hospitalised was -10.7 and days on IVs -20.2. Incremental cost was 3830 pounds. CONCLUSIONS: TNS was associated with clinically and socially important reductions of hospital attendances and parenteral antibiotics. This would improve patients' quality of life and reduce interference with work and schooling. Its maximal acquisition cost of 10,010 pounds may be reduced by delays in prescribing and dispensing, and was offset by savings of approximately 3500-6200 pounds.

Individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity and fewer associated costs.

STUDY OBJECTIVE: To examine the impact of individualized pharmacokinetic monitoring (IPM) on the development of aminoglycoside-associated nephrotoxicity (AAN). DESIGN: Retrospective case-control study. SETTING: Two teaching hospitals. SUBJECTS: Two thousand four hundred five patients who received aminoglycosides. INTERVENTION: Aminoglycoside therapy dosed by either IPM or physicians' directions. MEASUREMENTS AND MAIN RESULTS: Patients receiving IPM were significantly less likely to develop AAN by both univariate (7.9% vs 13.2%, p=0.02) and multivariate methods (odds ratio 0.42, p=0.002). Female sex was protective against AAN. Age 50 years and above, high initial aminoglycoside trough, long duration of therapy, and concurrent piperacillin, clindamycin, or vancomycin increased risk of AAN. We estimated that IPM decreased AAN costs by $90,995/100 patients. CONCLUSION: Individualized pharmacokinetic monitoring significantly decreased the frequency of AAN and its associated economic costs.

Comparative review of topical ophthalmic antibacterial preparations.

The choice of an antibacterial is based on considerations of pharmacodynamic, pharmacokinetic and bacteriological characteristics, risk of selecting resistant mutants, and cost. In this article we review 16 commercially available ophthalmic antibacterial preparations. Fusidic acid and bacitracin are selective for gram-positive bacteria whereas polymyxin B targets gram-negative species. Aminoglycosides and quinolones are broad spectrum antibacterials. The widespread use of an antibacterial increases risks of selecting resistance to it. Acquired resistance is well documented for fusidic acid and rifamycin, and newly described for quinolones. The bioavailability of an antibacterial agent depends on the target bacterial species, the site of infection and the integrity of the haemato-aqueous barrier. Some agents (fusidic acid, quinolones) penetrate the cornea, passing into the anterior chamber of normal eyes at therapeutic concentrations, whereas others (polymixin B, bacitracin) have no penetrating powers and remain at the surface of the eye. Toxicity is mostly manifested by allergic reactions to excipients or active ingredients in topical antibacterial preparations. A few cases of haematological toxicity have brought suspicion on topical chloramphenicol, but the link has yet to be proven. Erythromycin and polymyxin B are probably okay to use as topical applications in pregnant women and nursing mothers. Costs of treatment must be evaluated as a whole (regimen, drug associations). Prices for a bottle of eyedrops may vary 3-fold. The cheapest drugs include chloramphenicol, polymyxin B and gentamicin, the most expensive being fusidic acid and the quinolones.

Savings in direct medical costs from the use of tobramycin solution for inhalation in patients with cystic fibrosis.

OBJECTIVE: Two identical 24-week, double-blind, placebo-controlled trials of tobramycin solution for inhalation (TOBI [PathoGenesis Corporation, Seattle, Washington]) in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection were conducted in the United States. The aim of the present study was to extrapolate the US trial data to a Canadian setting, using Canadian costs to estimate the savings in direct medical costs that might result from use of a similar 24-week TOBI regimen versus usual care in 2 Canadian provinces. BACKGROUND: Cystic fibrosis is a genetic disease in which persistent respiratory infection, usually due to P. aeruginosa infection, is the major cause of morbidity and mortality. METHODS: The US trials demonstrated that TOBI produced significant improvements in pulmonary function test results, reduced sputum levels of P. aeruginosa, and resulted in a 26% reduction in the probability of hospitalization (95% CI, 2%-43% vs placebo in the clinical trials). Individual patient data from the US trials were used to calculate the mean number of days in hospital as well as the mean number of days of home intravenous or oral antibiotic therapy. To adjust for Canadian pricing, pertinent economic data were obtained from Statistics Canada and the Ontario and Quebec health ministries. Demographic and baseline data were obtained from health surveys conducted by the Canadian Cystic Fibrosis Foundation. RESULTS: Economic analysis showed that the use of TOBI for 24 weeks would result in estimated mean per-patient savings in direct medical costs (in Canadian dollars) of $4055 in Ontario and $4916 in Quebec, which would substantially offset the Canadian acquisition price of $8602 for the same 24-week period. CONCLUSIONS: Assuming that the percentage of reduction in hospital days observed in the US trials would also occur in the Canadian clinical setting, use of TOBI would reduce the use of health care services, particularly hospital days, and lead to substantial savings in direct medical costs that would offset its acquisition price. Whether this reduction actually occurs after TOBI enters the Canadian market is a subject for future investigation.

The economic impact of once-daily versus conventional administration of gentamicin and tobramycin.

This retrospective, observational study was designed to compare once-daily with conventional aminoglycoside administration for costs while determining equivalency in efficacy and toxicity. 100 consecutive patients who had been treated with once-daily aminoglycosides after 1st August 1993, were evaluated via retrospective chart review. For comparison, 100 consecutive patients who were treated with conventional regimens of aminoglycosides, over the same calender period 1 year earlier (beginning on 1st August 1992), were evaluated in a similar manner. Aminoglycoside antibacterials, excluding amikacin, were administered as a single daily dose of 6 mg/kg. 89 patients were cured or improved with once-daily administration versus 90 patients with conventional administration. One patient in each group developed definite aminoglycoside-induced renal toxicity. The total cost [in 1993 Canadian dollars ($Can)] per patient for once-daily and conventionally administered aminoglycosides was $Can97.62 and $ Can199.43, respectively. Thus, once-daily administration of aminoglycosides is as effective and well tolerated, while considerably less expensive than, aminoglycoside treatment utilising conventional regimens.

Once-daily aminoglycoside dosing: impact on requests and costs for therapeutic drug monitoring.

Recently, much interest has focused on the use of once-daily aminoglycosides (ODA) in the medical literature. In late 1992, we implemented a hospital-wide ODA program for adult patients at our 850-bed community-teaching hospital. In the first phase of implementation, therapeutic drug monitoring (TDM) was accomplished with the use of a random serum concentration and a nomogram that had been developed at our institution. In the second phase, serum drug concentrations were eliminated on patients with normal renal function. The fully implemented program resulted in a 40% decrease in the request for gentamicin and tobramycin serum concentrations as compared with historic ordering patterns for conventional aminoglycoside dosing regimens. In addition, the incidence of nephrotoxicity was also reduced from 3 to 5% with conventional aminoglycoside dosing, to 1.2 and 1.3% for phases 1 and 2, respectively. Furthermore, the elimination of TDM requests totaling 300 for gentamicin and 50 for tobramycin per month is expected to result in an annual institutional savings of > $100,000.

Cost analysis of imipenem-cilastatin versus clindamycin with tobramycin in the treatment of acute intra-abdominal infection.

Clinical effectiveness of imipenem/cilastatin (I/C) versus tobramycin with clindamycin (T + C) in treatment of patients presenting with suspected acute intra-abdominal infection was assessed in a multicentre randomised clinical trial conducted during 1985 to 1986. The principal finding was a lower incidence of treatment failure among patients in the I/C arm (p = 0.043). We now report results of retrospective analysis of hospital treatment costs during an episode of infection incurred by patients enrolled in the trial. Treatment costs (in 1989 US dollars) were calculated from a hospital perspective, using an intention-to-treat analysis. Among 161 patients with low illness severity (APACHE II less than or equal to 14) the mean cost for the episode of care was $US7038 in the I/C arm versus $US8404 for the T + C regimen; the difference was not statistically significant (p = 0.40). For 93 more severely ill patients (APACHE II score greater than 14) the mean cost for the I/C arm was $US19 985 versus $US16 582 for the T + C regimen; the difference was not statistically significant (p = 0.36). Multiple regression analysis, controlling for patient demographics and study site, showed that the cost of the episode was positively associated with the severity of illness (p less than 0.01) and presence of malnutrition (p < 0.01), but that the total cost of the episode of infection was not statistically different for the 2 drug regimens (p = 0.45).