The effect of generic market entry on antibiotic prescriptions in the United States.

When patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)-aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin-and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed.

Economic analysis of ceftaroline fosamil for treating community-acquired pneumonia in Spain.

Background: Adults admitted to hospital with community-acquired pneumonia (CAP) impose significant burden upon limited hospital resources. To achieve early response and possibly early discharge, thus reducing hospital expenditure, the choice of initial antibiotic therapy is pivotal.Methods: A cost-consequences model was developed to evaluate ceftaroline fosamil (CFT) as an alternative to other antibiotic therapies (ceftriaxone, co-amoxiclav, moxifloxacin, levofloxacin) for the empiric treatment of hospitalized adults with moderate/severe CAP (PORT score III-IV) from the perspective of the Spanish National Health System (NHS).Findings: Compared with ceftriaxone, the model predicted an increase in the number of CFT-treated patients discharged early (PDE) (30.6% vs. 26.1%) while decreasing initial antibiotic failures (3.8% vs. 7.6%). For patients with pneumococcal pneumonia, CFT was cost-saving vs. ceftriaxone (by 1.2%) and significantly increased PDE (32.1% vs. 24.6%). CFT resulted in cost-saving vs. levofloxacin, due lower initial antibiotic therapy costs and increased PDE (30.6% vs. 14.9%). Moxifloxacin and co-amoxiclav early response rate of 53.63% and 54.24% resulted in cost neutrality vs. CFT, with direct comparison hampered by the significantly different early response criteria utilized in the literature.Conclusions: Despite a higher unit cost, CFT is a reasonable alternative to other agents for adults hospitalized with moderate/severe CAP, given the projected higher PDE achieved with similar or lower total costs.

Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI).

Background: The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy. Methods: A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor. Results: In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = - 0.38 and ∆ = - 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy. Conclusions: The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.

Impact of an infectious diseases specialist-led antimicrobial stewardship programmes on antibiotic use and antimicrobial resistance in a large Korean hospital.

The aim of this study was to evaluate the impact of an infectious diseases specialist (IDS)-led antimicrobial stewardship programmes (ASPs) in a large Korean hospital. An interrupted time series analysis assessing the trends in antibiotic use and antimicrobial resistance rate of major pathogens between September 2015 and August 2017 was performed in an 859-bed university-affiliated hospital in Korea. The restrictive measure for designated antibiotics led by an IDS reduced carbapenems usage by -4.57 days of therapy (DOT)/1,000 patient-days per month in general wards (GWs) (95% confidence interval [CI], -6.69 to -2.46; P < 0.001), and by -41.50 DOT/1,000 patient-days per month in intensive care units (ICUs) (95% CI, -57.91 to -25.10; P < 0.001). Similarly, glycopeptides usage decreased by -2.61 DOT/1,000 patient-days per month in GWs (95% CI, -4.43 to -0.79; P = 0.007), and -27.41 DOT/1,000 patient-days per month in ICUs (95% CI, -47.03 to -7.79; P = 0.009). Use of 3rd generation cephalosporins, beta-lactam/beta-lactamase inhibitors, and fluoroquinolones in GWs showed change comparable with that of carbapenems or glycopeptides use. Furthermore, trends of antimicrobial resistance rate of Staphylococcus aureus to gentamicin in GWs, Staphylococcus aureus to ciprofloxacin and oxacillin in ICUs, and Pseudomonas aeruginosa to imipenem in ICUs decreased in slope in the intervention period. The in-hospital mortality rate per 1,000 patient-days among ICU patients remained stable between the pre-intervention and intervention periods. In conclusion, an IDS-led ASPs could enact a meaningful reduction in antibiotic use, and a decrease in antibiotic resistance rate, without changing mortality rates in a large Korean hospital.

Adding Azithromycin to Cephalosporin for Cesarean Delivery Infection Prophylaxis: A Cost-Effectiveness Analysis.

OBJECTIVE: To investigate the cost-effectiveness of adding azithromycin to standard cephalosporin regimens of cesarean delivery prophylaxis by considering the maternal outcomes in the current and potential subsequent pregnancies. METHODS: A cost-effectiveness model was created using TreeAge to compare the outcomes of using azithromycin-cephalosporin with cephalosporin alone in a theoretical cohort of 700,000 women, the approximate number of nonelective cesarean deliveries annually in the United States that occur during labor or after membrane rupture. Outcomes examined included endometritis, wound infection, sepsis, venous thromboembolism, and maternal death in the current pregnancy and uterine rupture, cesarean hysterectomy, and maternal death in subsequent pregnancies, including cost and quality-adjusted life-years for both pregnancies. Probabilities, utilities, and costs were derived from the literature, and a cost-effectiveness threshold was set at $100,000 per quality-adjusted life-year. Sensitivity analyses were used to determine the robustness of our results. RESULTS: Compared with cephalosporin alone for prophylaxis, our model showed 16,100 fewer cases of endometritis, 17 fewer cases of sepsis, eight fewer cases of venous thromboembolism, and one fewer maternal death with azithromycin-cephalosporin. Additionally, this strategy prevented 36 uterine ruptures and four cesarean hysterectomies in the subsequent pregnancy. Overall, the addition of azithromycin led to both lower costs and higher quality-adjusted life-years when compared with standard cephalosporin prophylaxis. In sensitivity analysis, we found that as long as the cost of azithromycin remained below $930 (baseline cost $27), it was cost-effective. CONCLUSION: For women who undergo cesarean delivery in labor or after membrane rupture, compared with cephalosporin alone, the addition of azithromycin to cesarean delivery infection prophylaxis is less costly and leads to better maternal outcomes in the index delivery and subsequent deliveries. These findings support the use of prophylactic azithromycin at the time of cesarean delivery.

Cost-effectiveness of ceftolozane/tazobactam plus metronidazole compared with piperacillin/tazobactam as empiric therapy for the treatment of complicated intra-abdominal infections based on the in-vitro surveillance of bacterial isolates in the UK.

AIMS: An increase in the prevalence of antimicrobial resistance among gram-negative pathogens has been noted recently. A challenge in empiric treatment of complicated intra-abdominal infection (cIAI) is identifying initial appropriate antibiotic therapy, which is associated with reduced length of stay and mortality compared with inappropriate therapy. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam (commonly used in this indication) in the treatment of patients with cIAI in UK hospitals. METHODS: A decision-analytic Monte Carlo simulation model was used to compare costs (antibiotic and hospitalization costs) and quality-adjusted life years (QALYs) of patients infected with gram-negative cIAI and treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Bacterial isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients in the UK infected with gram-negative pathogens. Susceptibility to initial empiric therapy was based on the measured susceptibilities reported in the PACTS database. RESULTS: Ceftolozane/tazobactam + metronidazole was cost-effective when compared with piperacillin/tazobactam, with an incremental cost-effectiveness ratio (ICER) of £4,350/QALY and 0.36 hospitalization days/patient saved. Costs in the ceftolozane/tazobactam + metronidazole arm were £2,576/patient, compared with £2,168/patient in the piperacillin/tazobactam arm. The ceftolozane/tazobactam + metronidazole arm experienced a greater number of QALYs than the piperacillin/tazobactam arm (14.31/patient vs 14.21/patient, respectively). Ceftolozane/tazobactam + metronidazole remained cost-effective in one-way sensitivity and probabilistic sensitivity analyses. CONCLUSIONS: Economic models can help to identify the appropriate choice of empiric therapy for the treatment of cIAI. Results indicated that empiric use of ceftolozane/tazobactam + metronidazole is cost-effective vs piperacillin/tazobactam in UK patients with cIAI at risk of resistant infection. This will be valuable to commissioners and clinicians to aid decision-making on the targeting of resources for appropriate antibiotic therapy under the premise of antimicrobial stewardship.

Cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam as empiric therapy based on the in-vitro surveillance of bacterial isolates in the United States for the treatment of complicated urinary tract infections.

BACKGROUND: A challenge in the empiric treatment of complicated urinary tract infection (cUTI) is identifying the initial appropriate antibiotic therapy (IAAT), which is associated with reduced length of stay and mortality compared with initial inappropriate antibiotic therapy (IIAT). We evaluated the cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam (one of the standard of care antibiotics), for the treatment of hospitalized patients with cUTI. METHODS: A decision-analytic Monte Carlo simulation model was developed to compare the costs and effectiveness of empiric treatment with either ceftolozane/tazobactam or piperacillin/tazobactam in hospitalized adult patients with cUTI infected with Gram-negative pathogens in the US. The model applies the baseline prevalence of resistance as reported by national in-vitro surveillance data. RESULTS: In a cohort of 1000 patients, treatment with ceftolozane/tazobactam resulted in higher total costs compared with piperacillin/tazobactam ($36,413 /patient vs. $36,028/patient, respectively), greater quality-adjusted life years (QALYs) (9.19/patient vs. 9.13/patient, respectively) and an incremental cost-effectiveness ratio (ICER) of $6128/QALY. Ceftolozane/tazobactam remained cost-effective at a willingness to pay of $100,000 per QALY compared to piperacillin/tazobactam over a range of input parameter values during one-way and probabilistic sensitivity analysis. CONCLUSIONS: Model results show that ceftolozane/tazobactam is likely to be cost-effective compared with piperacillin/tazobactam for the empiric treatment of hospitalized cUTI patients in the United States.

Ceftaroline fosamil use in hospitalized patients with acute bacterial skin and skin structure infections: Budget impact analysis from a hospital perspective.

PURPOSE: The budgetary impact of adding ceftaroline fosamil to a hospital formulary for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) was evaluated. METHODS: A three-year hospital budget impact model was constructed with three initial treatment options for ABSSSIs: ceftaroline fosamil, vancomycin plus aztreonam, and other vancomycin-containing regimens. The target population was hospitalized adult patients with an ABSSSI. Clinical cure rates with initial treatment were assumed to be similar to those from ceftaroline fosamil clinical trials. Patients who did not respond to initial treatment were assumed to be treated successfully with second-line antimicrobial therapy. Length of stay and cost per hospital day (by success or failure with initial treatment) were estimated based on a large database from more than 100 U.S. hospitals. Other model inputs included the annual number of ABSSSI admissions, projected annual case growth rate, proportion of ABSSSI target population receiving vancomycin-containing regimen, expected proportion of ABSSSI target population to be treated with ceftaroline fosamil, drug acquisition cost, cost of antibiotic administration, and cost of vancomycin monitoring. Sensitivity analysis using 95% confidence limits of clinical cure rates was also performed. RESULTS: The estimated total cost of care for treating a patient with an ABSSSI was $395 lower with ceftaroline fosamil ($15,087 versus $15,482) compared with vancomycin plus aztreonam and $72 lower ($15,087 versus $15,159) compared with other vancomycin-containing regimens. CONCLUSION: Model estimates indicated that adding ceftaroline fosamil to the hospital formulary would not have a negative effect on a hospital's budget for ABSSSI treatment.

Drug use evaluation of cefepime in the first affiliated hospital of Bengbu medical college: a retrospective and prospective analysis.

BACKGROUND: Cefepime is a fourth generation cephalosporin antimicrobial. Its extended antimicrobial activity and infrequent tendency to engender resistance make it popular for the treatment of infections. However, proper use of cefepime has not been studied adequately. In this study, we used a retrospective cohort and a prospective cohort to evaluate the usage pattern, adverse effects and cost-effectiveness of cefepime by conducting a drug use evaluation (DUE) program in the First Affiliated Hospital of Bengbu Medical College, Anhui, China. METHODS: The DUE criteria for cefepime were established by applying literature review and expert consultation, an effective method to promote interventions that will improve patient outcomes and the cost-effectiveness of drug therapy. According to the criteria, we performed a cross-sectional retrospective (cycle A) study on 96 hospitalized patients who received cefepime treatment and a prospective (cycle B) study on 111 hospitalized patients with cefepime treatment intervention. After identifying problems with usage and completing a cefepime use evaluation for cycle A, 2 months of educational intervention among professionals were given and a more effective and rational system of cefepime use was set up. During the 2 months, the lectures were arranged and attendance of prescribers was required. RESULTS: The data from cycle A showed that the biggest problem was irrational prescription of cefepime; bacterial culture and drug sensitivity tests for cefepime were also not carried out. Following 2 months of educational intervention among professionals, the results for cycle B showed that the correct indication rate was 94.59%, compared with 84.38% in cycle A. Use of bacterial culture and sensitivity tests also improved, by 88.29% in cycle B compared with 65.22% in cycle A. Compared with cycle A, the significantly improved items (P < 0.05) in cycle B were blood examination, liver function monitoring, renal function monitoring, dose and duration, dosing frequency and correct medication combinations. CONCLUSIONS: Cefepime can be used appropriately for the right indications and in a cost-effective way for the majority of patients through educational intervention, including the special precautions that must be followed for appropriate dosing frequency and duration. DUE programs will become one model of hospital pharmacy care and part of the plan for continuous improvements to the quality of health care in China.

The impact of pricing and patent expiration on demand for pharmaceuticals: an examination of the use of broad-spectrum antimicrobials.

The aim of the analysis was to determine whether demand in Germany for specific antimicrobial agents is driven by prices that drop considerably when generic substitutes become available. A time-series approach was therefore carried out to explore price elasticities of demand for two different classes of broad-spectrum antimicrobials (fluoroquinolones and cephalosporins) using data on ambulatory antibiotics prescribed on the German statutory health insurance scheme and data on in-hospital antibiotic use in a German teaching hospital. In short, we attempted to explain demand for different antibiotics based on changes in price and hospital-wide morbidity. The data indicate that patent expiration is followed by substantial decreases in the price of antibiotics. In the outpatient sector, all antibiotics included in the analysis showed significant negative own-price elasticities of demand. However, in the hospital settings, significant own-price elasticities were only determined for some antibiotics, although price decreases were stronger than in the outpatient sector. We conclude that price dependence of demand for antimicrobials is present both in the ambulatory and the hospital setting. However, this is especially surprising in the hospital setting because price differences among the antibiotics observed are particularly small compared with the overall cost of hospitalisation.

Comparison of enrofloxacin and ceftiofur sodium for the treatment of relapse of undifferentiated fever/bovine respiratory disease in feedlot cattle.

This commercial field trial compared the efficacy of enrofloxacin and ceftiofur sodium in beef cattle at high risk of developing undifferentiated fever (UF), also known as bovine respiratory disease (BRD) that received tilmicosin at feedlot arrival, were diagnosed and initially treated for UF with tilmicosin, and subsequently required a second UF treatment (first relapse). Feedlot cattle (n = 463) were randomly assigned to 2 experimental groups: ENRO or CEF. Second UF relapse, 3rd UF relapse, overall case fatality and BRD case fatality rates were lower in the ENRO group than in the CEF group (P < 0.05). There were no differences in average daily gain (allocation to re-implant date), chronicity, histophilosis case fatality or miscellaneous case fatality rates between the groups (P ≥ 0.05). A per-animal economic advantage of Can$57.08 was calculated for the ENRO group versus the CEF group. In feedlot cattle in western Canada at high risk of developing UF, it was more cost effective to administer enrofloxacin than ceftiofur sodium for treatment of UF relapse.

Changes in the use of broad-spectrum antibiotics after cefepime shortage: a time series analysis.

The original cefepime product was withdrawn from the Swiss market in January 2007 and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa toward carbapenems, ceftazidime, and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

The impact of a nationwide antibiotic restriction program on antibiotic usage and resistance against nosocomial pathogens in Turkey.

PURPOSE: Antimicrobial resistance among microorganisms is a global concern. In 2003, a nationwide antibiotic restriction program (NARP) was released in Turkey. In this study we evaluated the effect of NARP on antibiotic consumption, antimicrobial resistance, and cost. MATERIALS AND METHODS: The data obtained from all of the four university hospitals, and one referral tertiary-care educational state hospital in Ankara. Antimicrobial resistance profiles of 14,233 selected microorganisms all grown in blood cultures and antibiotic consumption from 2001 to 2005 were analyzed retrospectively. RESULTS: A negative correlation was observed between the ceftriaxone consumption and the prevalence of ceftriaxone resistant E.coli and Klebsiella spp. (rho:-0.395, p:0.332 and rho:-0.627, p:0.037, respectively). The decreased usage of carbapenems was correlated with decreased carbapenems-resistant Pseudomonas spp. and Acinetobacter spp (rho:0.155, p:0.712 and rho:0.180, p:0.668, respectively for imipenem). Methicillin resistance rates of S.aureus were decreased from 44% to 41%. After two years of NARP 5,389,155.82 USD saving occurred. CONCLUSION: NARP is effective in lowering the costs and antibiotic resistance.

An economic model for the prevention of MRSA infections after surgery: non-glycopeptide or glycopeptide antibiotic prophylaxis?

AIM: Surgical site infection is commonly caused by Staphylococcus aureus. The multiresistant strains (MRSA) are resistant to most antibiotic prophylaxis regimens. Our aim was to explore whether there is a threshold of MRSA prevalence at which switching to routine glycopeptide-based antibiotic prophylaxis becomes cost-effective. METHODS: An indicative model was designed to explore the cost-effectiveness of vancomycin, cephalosporin or a combination, in patients undergoing primary hip arthroplasty. RESULTS: If the MRSA infection rate is equal to or above 0.25% and the rate of other infections with cephalosporin prophylaxis is equal to or above 0.2%, use of the combination antibiotic prophylaxis is optimal. DISCUSSION: Modelling the cost-effectiveness of interventions for MRSA prevention is complex due to uncertainty around resistance and effectiveness of glycopeptides. CONCLUSIONS: The indicative model provides a framework for evaluation. More work is needed to understand the impact of antibiotic resistance over time in these currently effective antibiotics.

[Estimation of the clinical and pharmacoeconomic efficiency of treatment in patients with community-acquired pneumonia with third-generation cephalosporins].

The clinical and pharmacoeconomic effectiveness of the third-generation cephalosporin Ceftriabol versus the original drug Claforan in the treatment of varying community-acquired pneumonia was studied in 60 and 58 patients, respectively. The Russian third-generation cephalosporin Ceftriabol was shown to be as effective as Claforan in treating patients with community-acquired pneumonia. However, in addition to the main--therapeutic effect, Ceftriabol produces a certain economic gain.

A systematic review and economic model of switching from non-glycopeptide to glycopeptide antibiotic prophylaxis for surgery.

OBJECTIVES: To determine whether there is a level of methicillin-resistant Staphylococcus aureus (MRSA) prevalence at which a switch from non-glycopeptide to glycopeptide antibiotics for routine prophylaxis is indicated in surgical environments with a high risk of MRSA infection. DATA SOURCES: Major electronic databases were searched up to September 2005. REVIEW METHODS: The effectiveness review included controlled clinical trials comparing a glycopeptide with an alternative antibiotic regimen that reported effectiveness and/or adverse events. Controlled observational studies were also included for adverse events. The cost-effectiveness review included economic evaluations comparing glycopeptide prophylaxis with any alternative comparator. Study validity was assessed using standard checklists. The supplementary economic reviews assessed evaluations of non-glycopeptide antibiotic prophylaxis; evaluations where antibiotic resistance is a problem; methods of modelling resistance in infectious diseases; and developing a conceptual framework. An indicative decision analytic model was developed to compare vancomycin with a cephalosporin and with a combination of vancomycin and cephalosporin, using hip arthroplasty as an exemplar. Available data on, for example, surgical site infection (SSI) rates, MRSA rates, effectiveness of the antibiotics, were incorporated into the model. Costs were estimated from the perspective of the NHS. RESULTS: The effectiveness review included 16 randomised controlled trials, with a further three studies included for adverse events only. There was no evidence that glycopeptides were more effective than non-glycopeptides in preventing SSIs. Most of the trials did not report either the baseline prevalence of MRSA at the participating surgical units or MRSA infections as an outcome. The cost-effectiveness review included five economic evaluations of glycopeptide prophylaxis. Only one study incorporated health-related quality of life and undertook a cost-utility analysis. None of the studies was undertaken in the UK and none explicitly modelled antibiotic resistance. The supplementary reviews provided few insights into how to assess cost-effectiveness in the context of resistance. No studies modelled cost-effectiveness alongside epidemiological models of resistance. There was little information regarding the impact of surgical infections on costs post-discharge and patient quality of life. The lack of available clinical evidence limited the development of the cost-effectiveness model and meant that the modelling could only be indicative in nature. The model can be used to show the threshold baseline risk at which the use of vancomycin as prophylaxis might be cost-effective (the model did not include teicoplanin). The indicative model suggests that the baseline risk of MRSA can be fairly modest at below the national average and it would still appear cost-effective to use glycopeptide prophylaxis. The model indicates that the use of glycopeptides as a form of prophylaxis in addition to a treatment for MRSA infections is unlikely to decrease the total usage and hence reduce the risk of future problems with glycopeptide-resistant bacteria. CONCLUSIONS: There is insufficient evidence to determine whether there is a threshold prevalence of MRSA at which switching from non-glycopeptide to glycopeptide antibiotic prophylaxis might be clinically effective and cost-effective. Future research needs to address the complexities of decision-making relating to the prevention of MRSA and infection control in general. Research including evidence synthesis and decision modelling comparing a full range of interventions for infection control, which extends to other infections, not just MRSA, is needed. A long-term research programme to predict the pattern of drug resistance and its implications for future costs and health is also needed.

Once-daily cefepime versus ceftriaxone for nursing home-acquired pneumonia.

OBJECTIVES: To compare once-daily intramuscular cefepime with ceftriaxone controls. DESIGN: Double-blind study. SETTING: Six skilled nursing facilities. PARTICIPANTS: Residents aged 60 and older with nursing home-acquired pneumonia. INTERVENTION: Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours. MEASUREMENTS: Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed. RESULTS: Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age+/-standard deviation of 85+/-6, with a mean 5.8+/-1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35+/-7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were 117+/-40 dollars for cefepime- and 215+/-68 dollars for ceftriaxone-treated patients (P<.001). Cost-effectiveness analysis of total costs showed that cefepime would cost 597 dollars and ceftriaxone 1,709 dollars per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust. CONCLUSIONS: Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization.