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Background The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT). Methods Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221‐C‐001 trial and SoC outcomes obtained from a real‐world chart review of patients in France. Results Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61–1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47–0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72–13.24) and 4.76 months for SoC (95% CI, 3.81–8.21). Results remained robust across all sensitivity analyses conducted. Conclusions PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes., Overall survival was improved with enasidenib compared with SoC. Enasidenib may be an important advance in treatment for patients with R/R acute myeloid leukemia associated with IDH2 mutations who are ineligible for hematopoietic stem cell transplantation.

Mobilization and collection of peripheral blood stem cells is part of the standard treatment procedure for non-Hodgkin’s lymphoma patients eligible for high-dose chemotherapy with autologous stem cell transplantation. Mobilization is usually achieved with chemotherapy and/or cytokines, but plerixafor might be added in case of poor mobilization. Due to the high cost several institutions have developed their own management pathway to optimize use of plerixafor. Such models are however rarely generalizable; in a multi-center, European, non-interventional study, evaluating the impact of plerixafor in poor mobilizers, country specific differences in patient treatment and cost structure were obvious. For German centers, there was a non-significant reduction in the number of apheresis sessions carried out and in apheresis costs. In contrast to other European countries the majority of German Plerixafor patients were very poor mobilizing patients with initial CD34+ cell count ≤ 10/µl (40/51). In this group the number of apheresis sessions decreased from 2.1 to 1.6 sessions per patient (p = 0.01) and costs decreased from €6246 to €4758 (p = 0.01). Our results show that preemptive plerixafor use has a strong effect in poor mobilizers with an initial CD34+ cell count ≤ 10 cells/µl. CA extern

Background: A European Marketing Authorization Application for ivosidenib (IVO) is currently under review for the indication of mutant isocitrate dehydrogenase 1 (mIDH1) R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) in adult patients (pts) who have received ≥ 2 prior regimens, including ≥ 1 standard intensive chemotherapy (IC) regimen, or are not candidates for IC and have received ≥ 1 prior non-intensive regimen. IVO is an oral, potent, targeted inhibitor of mIDH1 and was approved by the FDA for the treatment of mIDH1 R/R AML in 2018, and in newly diagnosed AML in adults ≥ 75 years of age or pts ineligible for IC in 2019, based on the results of the open-label AG120-C-001 (NCT02074839) study. Aims: To evaluate the comparative benefit of IVO within the proposed EU indication, matched pt analyses were conducted using data on mIDH1 R/R AML pts from the AML Study Group (AMLSG) registry (NCT01252485) and a real-world chart review study (RWD) from France, Germany, UK, and Spain. Methods: Individual pt data from Arm 1+ of the AG120-C-001 study (n = 159) was compared to a historical control (HC), combining individual pt data from the AMLSG registry (n = 127) and the RWD (n = 148). A medical review was conducted to identify Arm 1+ IVO pts in the AG120-C-001 study and HC pts who fell within the proposed EU indication. Treatment with IVO was compared with the most recent therapy received by HC pts. HC pts treated with IC as their most recent therapy were excluded, as IVO pts, based on the AG120-C-001 study's eligibility criteria, were not considered candidates for IC. Propensity score-based matching/weighting methods were used to adjust for imbalances in baseline prognostic factors between the 2 cohorts (optimal full matching and inverse probability of treatment weighting [IPTW]). A literature review and data availability led to the inclusion of 6 baseline prognostic factors for estimation of propensity scores (age, history of hematopoietic stem cell transplantation, number of prior regimens for AML, nature of AML, cytogenetic risk, and primary refractory status). Balance between populations was assessed pre- and post-match via comparison of (weighted) standardized differences (SDs) for each covariate. Time-to-event data were summarized via Kaplan-Meier (KM) estimators with 2-sided 95% confidence intervals (CI). Cox regression analysis, using the key prognostic factors as covariates, was applied to estimate hazard ratios (HR) of overall survival (OS), and the corresponding 95% CI was estimated using the sandwich estimator. Complete remission (CR) rates were also compared between IVO pts and RWD non-IC HC pts (AMLSG pts were excluded as the response data did not allow for identification of CRs distinct from other response types). Results: One hundred and nine IVO pts and 60 HC pts fell within the proposed EU indication. The IPTW-matched dataset was selected for analysis, as it more strongly minimized the absolute weighted SDs between cohorts as compared with optimal full matching, with all SDs < 0.05. Median OS was 8.1 months (mo) (95% CI: 5.7, 9.8) with IVO compared with 2.9 mo (95% CI: 1.9, 4.5) in the HC pts. The HR for OS was 0.396 (95% CI: 0.279, 0.562), strongly in favor of IVO (p < 0.0001). There was clear and early separation of the IVO and HC KM curves, reflecting the early and sustained benefit of IVO treatment in this setting (Fig). Six- and 12-mo survival rates in the IVO cohort were 57.7% (95% CI: 48.2, 67.2) and 35.0% (95% CI: 25.7, 44.3), respectively, representing improvements versus 6- and 12-mo survival rates in the HC cohort of 29.1% (95% CI: 17.4, 40.8) and 10.8% (95% CI: 2.7, 18.9), respectively. The IVO cohort also demonstrated higher rates of CR than the HC cohort, with an observed CR rate of 18.3% (95% CI: 11.6, 26.9), compared with 7.0% (95% CI: 1.5, 19.1). Conclusion: IVO monotherapy demonstrated prolonged OS and the potential to increase CR rates vs standard of care therapies in a HC population. Disclosures Paschka: Amgen: Other; AbbVie: Other: Travel, accommodation or expenses, Speakers Bureau; Astellas Pharma: Consultancy, Speakers Bureau; Celgene: Consultancy, Other: Travel, accommodations or expenses; Sunesis Pharmaceuticals: Consultancy; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Otsuka: Consultancy; Janssen Oncology: Other; Astex Pharmaceuticals: Consultancy; Agios Pharmaceuticals: Consultancy, Speakers Bureau; BerGenBio ASA: Research Funding. Dombret:Novartis: Consultancy; Cellectis: Consultancy; Sunesis: Consultancy; Abbvie: Consultancy; Immunogen: Consultancy; Celgene: Honoraria; Amgen: Consultancy, Honoraria; Jazz Pharma: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Shire: Honoraria; Otsuka: Consultancy, Honoraria; Menarini: Honoraria; Daiichi Sankyo: Consultancy, Other: travel, accommodation expenses; Incyte: Consultancy, Other: travel, accommodation expenses; Celyad: Consultancy. Montesinos Fernandez:Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vyas:Astellas: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Forty Seven: Research Funding; Pfizer: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; AbbVie: Speakers Bureau. Kreuzer:Daiichi Sankyo: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Chugai: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Grifols: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Hexal: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Otsuka: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Ariad: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Baxalta: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau; Biotest: Consultancy, Honoraria, Other: Personal fees, Research Funding, Speakers Bureau. Heuser:Karyopharm: Research Funding; Janssen: Consultancy; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Abbvie: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; BerGenBio ASA: Research Funding; Bayer: Consultancy, Research Funding; PriME Oncology: Honoraria. Metzeler:Daiichi Sankyo: Honoraria; Otsuka Pharma: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy; Astellas: Honoraria. Quesnel:Abbvie: Other: travel expenses; Daichii Sankyo: Other: travel expenses, Research Funding. Mohty:Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. De Botton:Pierre Fabre: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Servier: Consultancy; Celgene: Consultancy, Honoraria, Speakers Bureau; Agios: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Syros: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Seattle Genetics: Honoraria; Janssen: Consultancy, Honoraria. Döhner:Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Consultancy; Astellas Pharma: Consultancy; Astex Pharmaceuticals: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Sunesis Pharmaceuticals: Research Funding; Janssen: Consultancy, Honoraria; Agios: Consultancy; Novartis: Honoraria, Research Funding; Abbvie: Consultancy. Milkovich:RJM Group LLC: Current Employment. Reitan:RJM Group LLC: Current Employment. MacDonald:IQVIA: Current Employment. Casso:IQVIA: Current Employment. Storm:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Liu:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Kapsalis:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Attar:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Winkler:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Döhner:Agios: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Astex: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Oxford Biomedicals: Consultancy, Honoraria; Helsinn: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Sunesis: Other, Research Funding.

High-dose chemotherapy alongside peripheral blood stem cell (PBSC) infusion has become the standard of care in different hematologic malignancies. The goal of PBSC mobilization is to allow collection of sufficient CD34+ cells to proceed to transplantation. The current mobilization regimen with granulocyte colony-stimulating factor (G-CSF), alone or in combination with chemotherapy, still fails in 10-25% of patients. Plerixafor is able to rescue most of these patients from mobilization failure. In this study, we investigated the impact of plerixafor on the cost and time spent on apheresis in patients who were considered poor mobilizers, with

Background: Autologous hematopoietic stem cell transplantation (ASCT) is the current standard of care in patients with multiple myeloma (MM) to support reconstitution of the bone marrow after myeloablative chemotherapy. Mobilization of blood progenitor cells to the peripheral circulation is stimulated via administration of granulocyte colony-stimulating factor (G-CSF) with or without chemotherapy. The addition of chemotherapy, typically cyclophosphamide, increases the yield of peripheral blood stem cells (also known as CD34+ cells) at the expense of additional toxicity. The unpredictability of harvest yield and the potential need for weekend apheresis sessions complicates mobilization planning when using chemotherapy. Plerixafor, a CXCR4 antagonist, in combination with G-CSF has been shown to be superior to G-CSF alone, leading to higher CD34+ yields in fewer apheresis sessions [Giralt et al, 2014]. However, the advantage of the combination of plerixafor with G-CSF is less well described in the context of new treatment options that can impair stem cell harvest yields when using G-CSF as the sole mobilization agent. Objective: The primary objective of this study was to determine clinical outcomes associated with G-CSF alone vs G-CSF + chemomobilization vs G-CSF + plerixafor from initiation of mobilization until 6 to 12 months after ASCT. Method: This is a retrospective study in patients with MM, carried out at 10 centers in the US. Patients were eligible if ≥ 18 years and undergoing first ASCT (≤ 12 months from initial diagnosis and no disease progression). Eligible patients were identified through a database query of hospital records of oncology patients diagnosed with MM and eligible for ASCT before June 2016. Patients fulfilling inclusion and exclusion criteria were attributed to three treatment arms depending on the mobilization regimen received:Arm 1: G-CSF + plerixaforArm 2: G-CSF + chemomobilizationArm 3: G-CSF Patients will be selected until 170 patients are assigned to each treatment arm or patient records are exhausted. Demographics, induction regimen, mobilization regimens and outcomes, apheresis, transplantation outcomes and survival status were extracted from medical charts and entered in the electronic case report form. Here, we present interim results from data collected at three centers as of June 24, 2019. Results: At the interim analysis cut-off date, 130 patients were included in the database (G-CSF: 52; G-CSF + plerixafor: 78; G-CSF + chemomobilization: 0). Demographic and baseline characteristics were comparable between the two treatment arms. More male patients were included (male: 63%, female: 37%) and the mean age was 58 and 59 years in the G-CSF and G-CSF + plerixafor groups, respectively (Table 1). Disease stage and the proportion of patients with poor-, intermediate- and high-cytogenetic risk status were similar in the two treatment groups. Few patients had a complete response (CR) after chemotherapy, but response rate (CR + partial response) was 91% in both treatment arms. The burden of apheresis in terms of number of sessions and blood volume processed was lower in patients receiving G-CSF + plerixafor compared with patients receiving G-CSF only (Table 2). CD34+ yield was higher in the G-CSF + plerixafor treatment arm, especially after the first apheresis session (Table 2). There was no difference in ASCT outcome between the two treatment groups. All patients had neutrophil engraftment except for one patient in the G-CSF only group, and all patients had platelet engraftment except one patient in each treatment group. There was no significant difference in the proportion of patients experiencing relapse between the two treatment groups at 6 and 12 months of follow-up. Overall, ≥ 90% of patients avoided relapse at 12 months. 96% and 93% of patients were still alive at 12 months in the G-CSF only and G-CSF + plerixafor treatment groups, respectively (Table 3). For the purpose of this study, safety data was not reviewed [Mozobil PI, 2019]. Conclusions: Per interim results, plerixafor reduced the burden of apheresis and increased CD34+ yields. Transplantation outcomes, relapse and overall survival at 6 and 12 months were not significantly different between the two treatment arms. Therefore, plerixafor could increase apheresis efficiency without compromising ASCT success in the context of currently used chemotherapy regimens. Disclosures Mark: Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Bubalo:Sanofi: Other: Research and writing support. Barnes:Sanofi: Employment. Drea:Sanofi-Genzyme: Employment. Fausel:Sanofi-Genzyme: Other: Grant to cover costs of data collection.

A health economic analysis was undertaken based on the one-year database from a randomized study of rabbit anti-human thymocyte immunoglobulin (rATG) versus basiliximab, in kidney transplantation using resource utilization data and cost estimates from three German hospitals. A three-state Markov model was applied to estimate cost effectiveness to 10 years post-transplant. Total mean treatment cost per patient to year 1 post-transplant was €62,075 versus €59,767 for rATG versus basiliximab (p

To evaluate the time to symptom resolution and i.v.-to-p.o. transition in community-acquired pneumonia (CAP) patients treated with 750 mg or 500 mg levofloxacin.A retrospective, subset analysis of a multicenter, randomized, double-blind, controlled trial comparing 750 mg levofloxacin for 5 days to 500 mg levofloxacin for 10 days for the treatment of CAP.A total of 528 CAP patients were included. Baseline symptoms were re-evaluated on Day 3 of therapy, and time to i.v.-to-p.o. transition was recorded for inpatients.For the overall population, 67.4% of patients receiving 750 mg levofloxacin had resolution of fever by Day 3 of therapy, compared to 54.6% of 500 mg treated patients (P = 0.006). Patients who started on 750 mg levofloxacin i.v. (N = 108) transitioned to p.o. in an average of 2.68 days while those starting on 500 mg i.v. (N = 124) transitioned in 2.95 days (P = 0.144). The median time for i.v.-to-p.o. switch was 2.35 days and 2.75 days for patients receiving 750 mg and 500 mg levofloxacin, respectively (P = 0.098, log rank test). By Day 3 of therapy, 68% of patients receiving the 750 mg dose had transitioned from i.v. to p.o. levofloxacin, compared with 61% of the 500 mg group (P = 0.280). The safety profiles were comparable for the two regimens.The 750 mg levofloxacin dose resulted in a greater proportion of patients with resolution of CAP symptoms by Day 3 when compared with 500 mg therapy. Consequently, the 750 mg regimen trended toward more rapid transition to p.o., potentially resulting in lower overall drug costs. Time to switch from i.v. to p.o. was determined by the investigators' discretion rather than a set protocol. Additionally, length of stay data was not collected in this study, which can significantly impact overall healthcare costs. Further research is required to fully understand the economic impact of the 750 mg, 5-day levofloxacin regimen.

Objective. To quantify time expended, patient satisfaction, and econometrics associated with short-acting (sargramostim, epoetin alfa) and long-acting (darbepoetin alfa, pegfilgrastim) growth factors. Design. Retrospective resource utilization and prospective two-phase observational study. Methods. During week 1, time-motion measurements related to patient treatment and drug preparation were collected for scheduling; check-in; phlebotomy; laboratory; and drug preparation, administration, and recording. Drug utilization for one chemotherapy cycle during weeks 2 and 3 was assessed for sargramostim, pegfilgrastim, epoetin alfa, darbepoetin alfa, sargramostim plus epoetin alfa, and pegfilgrastim plus darbepoetin alfa. Patients completed a satisfaction survey. Results. Among 140 patients (mean age 58 yrs), mean chemotherapy cycle duration was 19 days. A total of 268 events were observed. Mean total staff time/patient visit for drug administration was 22.1 minutes, with most time spent on scheduling (5.5 min) and drug preparation, administration, recording (5.2 min). For sargramostim only versus pegfilgrastim only, pegfilgrastim resulted in a 37% reduction (p

The abilities of therapeutic interchange (TI) and standard educational tools (SET) to change prescribing habits were compared. We evaluated the replacement of ciprofloxacin with levofloxacin in a four-hospital health system during a 14-month study period. Two hospitals used TI and two SET. The demographics, sites of infection, and severity of illness were analyzed for 554 patients treated at SET hospitals and 1323 patients treated at TI hospitals during a total of 2040 hospitalizations over a 14-month period. In TI hospitals, 97% of patients received levofloxacin, whereas 43% received levofloxacin in SET hospitals (p < 0.001). Clinical outcomes were not significantly different for the two groups, although more patients in the SET hospitals received combination antimicrobial therapy. Differences in savings per patient were significant between TI hospitals ($60) and SET hospitals ($37) (p < 0.001). The total annualized savings for all four hospitals was $156,444. TI was more effective than SET in facilitating changes in prescribing patterns in a health care system and resulted in significant cost savings to hospitals and payers.

Study Objective. To compare rates of adverse events with filgrastim versus sargramostim when given prophylactically to patients receiving myelosuppressive chemotherapy. Design. Retrospective review with center crossover. Setting. Ten United States outpatient chemotherapy centers. Patients. Four hundred ninety patients treated for lung, breast, lymphatic system, or ovarian tumors. Intervention. Prophylactic use of filgrastim or sargramostim, with dosages at investigator discretion. Measurements and Main Results. The frequency and severity of adverse events and the frequency of switching to the alternative CSF were assessed. There was no difference in infectious fever. Fever unexplained by infection was more common with sargramostim (7% vs 1%, p

Skin and soft tissue infections (SSTI) are a common cause of antibiotic prescriptions and loss of time from school and work. Economic pressures on the delivery of healthcare have resulted in a focus on reducing resource utilization and costs, but not always on maintaining or improving the quality of patient care. The impact of treatment failure on the overall cost of therapy is not well reported for SSTI; however, older antibiotics, which can be perceived to be less expensive, may have a higher risk of treatment failure due to the development of resistance. This can increase overall direct and indirect treatment costs, including more office or emergency department visits for additional examinations/procedures, additional prescriptions for adjuvant therapies and supplementary antibiotics and, for some infections, hospitalization or increased length of hospital stay. Selection of antibiotics with an appropriate spectrum of activity is key, while the use of antibiotics with short and/or simple dosing regimens and a good tolerability profile, such as linezolid, which maximize patient adherence to the dosing regimen, can also play a role in ensuring that adequate antibiotic therapy is received. A further consideration is the time to symptom resolution, which can have a substantial impact on the patient's quality of life as well as affecting the indirect costs of the disease (e.g. loss of productivity and lost working days for the patient or parent). Thus, careful selection of antibiotic therapy, taking into account potential health outcomes and pharmacoeconomic benefits, is important to optimize clinical and bacteriological outcomes and thereby reduce overall costs to both the healthcare system and society.

The cost of outpatient parenteral antibiotic therapy is outweighed by the benefits to all involved: provider, payer, patient and society. Simple comparisons of inpatient and outpatient charges are not a true measure of costs. Recent in-depth cost-benefit analyses reveal a significant saving when indirect benefits, such as increased productivity and quality of life, are included. Even so, financial issues remain to be addressed.

The costs of outpatient parenteral antibiotic therapy are outweighed by the benefits to all involved: provider, payer, patient, and society. Simple comparisons of inpatient and outpatient charges are not a true measure of costs. Recent in-depth cost-benefit analyses reveal a significant saving when indirect benefits, such as increased productivity and quality of life, are included. Even so, financial issues remain to be addressed.

Two of the most serious respiratory tract infections are community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB). The most common pathogens found in patients with these infections are Haemophilus influenzae and Streptococcus pneumoniae. Pseudomonas aeruginosa is also relatively common, particularly in elderly patients with AECB. S. pneumoniae and P. aeruginosa are also of concern in relation to the development of resistance to antimicrobial drugs. The administration of antibiotics at doses that result in concentrations exceeding the mutant prevention concentration at the site of infection is one strategy to prevent the development of drug-resistant pathogens. AECB is associated with a high risk of in-hospital mortality, particularly in patients treated in the intensive care unit. CAP is also associated with significant risks and often requires treatment under hospital supervision. Several patient-related factors help identify those patients who are most at risk of mortality and morbidity. Treatment should be tailored towards the severity of the disease. The fluoroquinolones, such as levofloxacin, are an effective treatment option for AECB and CAP. Compared with many other antibiotics, resistance to levofloxacin remains low for most infecting pathogens. The oral bioavailability of levofloxacin is over 99%, enabling simple switching from intravenous to oral therapy during treatment. It is also preferentially distributed to compartments in the lung, thus achieving high concentrations at the site of respiratory tract infections. Combined with cover of the major infecting pathogens found in patients with AECB and CAP, and a cost-effective treatment compared with many alternative therapies, levofloxacin is an attractive option for the treatment of at-risk patients with these respiratory tract infections.

In response to the overuse and misuse of antibiotics, leading to increasing bacterial resistance and decreasing development of new antibiotics, the Council for Appropriate and Rational Antibiotic Therapy (CARAT) has developed criteria to guide appropriate and accurate antibiotic selection. The criteria, which are aimed at optimizing antibiotic therapy, include evidence-based results, therapeutic benefits, safety, optimal drug for the optimal duration, and cost-effectiveness.

There is limited experience in the healthcare field in terms of the evaluation of treatment costs. All too often, healthcare providers focus on the financial end-points (such as drug acquisition costs) as opposed to clinical end-points. This approach fails to view products from a broader perspective and tends to ignore the impact of a drug in terms of better patient compliance, fewer office visits, reduced length of hospital stay, or avoidance of hospitalisation. This article will briefly discuss the techniques used in the US to improve the utilisation of antibiotics, and describe the move towards the use of outpatient (i.e. outpatient care attached to a hospital, or in an infusion or clinic setting) or home therapy.

Economic pressures on the delivery of health care have necessitated a focus on reducing costs and resource utilization while maintaining or improving the quality of care. A growing consensus holds that switching from intravenous to oral therapy is a cost-effective and clinically sound approach for a significantly large group of patients with community-acquired pneumonia (CAP). Drug utilization studies within the INOVA Health System revealed that levofloxacin is a cost-effective alternative to ciprofloxacin in infectious disease and that use of risk prediction criteria can reduce inappropriate hospitalizations for CAP, thereby reducing costs. In addition, the INOVA experience demonstrates that the strategy used to implement new antibiotic regimens such as switch-therapy regimens is an important factor in cost reduction: a therapeutic interchange mandate is more successful than standard educational techniques in changing treatment patterns.

The pharmacist provides a vital role in the management of antibiotic policy. Consumers and payers demand quality care at a significantly reduced price. It is imperative that health care adapt to the times. Physicians must be involved in all phases of programmes that are viewed as cost saving. These programmes should integrate and document both clinical and financial aspects of care.

Radiographic confirmation of enteral feeding tube placement is a common practice representing considerable expense and causing delay in the initiation of enteral nutrition therapy. We evaluated an enteral feeding tube with a pH sensor, which allows immediate verification of the location of the tube by assessment of the pH upon insertion. Insertion pHs were obtained for 24 intensive care unit patients requiring feeding tube placement. Placement was verified radiographically and compared with expected location on the basis of the pH profile. The radiograph and the insertion pH profile were in agreement in 87.5% (21 of 24) of the cases. Concomitant use of histamine blockers did not affect the ability of the pH sensor to detect placement accurately (Fisher's Exact Test, p 5.71) Use of these pH measurements eliminates the need for radiographic documentation of placement, provides a savings for the patient, and may be beneficial in promoting enteral feedings in critically ill patients.

With the implementation of prospective payment (e.g. diagnosis-related groups [DRGs] and cost containment efforts, physicians and pharmacists have had to reevaluate current drug delivery systems in the search for the least costly means of administering parenteral products. The following describes a three-phase approach to fully assess relative antibiotic cost and to assess economic efficiencies of intramuscular and intravenous administration of antibiotics. Relative costs of therapy consist of acquisition cost, administration cost and total cost of self-administration. Various intravenous administration systems are described, as are considerations for intramuscular administration. Comparisons are made using intravenous and intramuscular administrations of cefazolin, gentamicin, penicillin and imipenem. Using a 'best case' scenario, the intramuscular route was found to be up to one tenth the expense of the intravenous route in certain instances. Also, the intramuscular route may facilitate early discharge and self-administration in the home. Antibiotics available for intramuscular injection should therefore be considered as an economically efficient alternative to intravenous injections, in appropriate patients.