Linezolid versus vancomycin cost in the treatment of staphylococcal pneumonia.

OBJECTIVE: Staphylococcusaureus is involved in around 20% of nosocomial pneumonia cases. Vancomycin used to be the reference antibiotic in this indication, but new molecules have been commercialized, such as linezolid. Previous studies comparing vancomycin and linezolid were based on models. Comparing their real costs from a hospital perspective was needed. METHODS: We performed a bicentric retrospective analysis with a cost-minimization analysis. The hospital antibiotic acquisition costs were used, as well as the laboratory test and administration costs from the health insurance cost scale. The cost of each hospital stay was evaluated using the national cost scale per diagnosis related group (DRG), and was then weighted by the stay duration. RESULTS: Fifty-eight patients were included. All bacteria identified in pulmonary samples were S. aureus. The cost of nursing care per stay with linezolid was €234.10 (SD=91.50) vs. €381.70 (SD=184.70) with vancomycin (P=0.0029). The cost of laboratory tests for linezolid was €172.30 (SD=128.90) per stay vs. €330.70 (SD=198.40) for vancomycin (P=0.0005). The acquisition cost of linezolid per stay was not different from vancomycin based on the price of the generic drug (€54.92 [SD=20.54] vs. €40.30 [SD=22.70]). After weighting by the duration of stay observed, the mean cost per hospital stay was €47,411.50 for linezolid and €57,694.0 for vancomycin (NSD). CONCLUSION: These results, in favor of linezolid, support other former pharmacoeconomic study based on models. The mean cost per hospitalization stay was not statistically different between the two study groups, but a trend in favor of linezolid is emerging.

Pharmacokinetic evaluation of linezolid administered intravenously in obese patients with pneumonia.

OBJECTIVES: Altered linezolid pharmacokinetics (PK) in obese individuals has been hypothesized in previous studies. However, specific dosing recommendations for this population are still lacking. The main goal of this study was to evaluate PK/pharmacodynamic (PKPD) target attainment when using a 600 mg intravenous q12h linezolid dose against MRSA in obese patients with pneumonia. METHODS: Fifteen obese pneumonia patients with a confirmed or suspected MRSA involvement treated with 600 mg of intravenous linezolid q12h were studied for 3 days. Population PK modelling was used to characterize the PK variability and to screen for influential patient characteristics. Monte Carlo simulations were carried out to investigate the PTA and time to target attainment for linezolid dosing against MRSA. RESULTS: A two-compartment model with linear elimination adequately described the data. Body weight and age both have a significant effect on linezolid clearance. Simulations demonstrate that the probability of attaining PKPD targets is low. Moreover, the PTA decreases with weight, and increases with age. Standard linezolid dosing in obese pneumonia patients with MRSA (MICs of 1-4 mg/L) leads to unacceptably low (near zero to 60%) PTA for patients <65 years old. CONCLUSIONS: Standard linezolid dosing is likely to provide insufficient target attainment against MRSA in obese patients. Body weight and especially age are important characteristics to be considered when administering linezolid to treat MRSA infections.

Effective Antimicrobial Stewardship Strategies for Cost-effective Utilization of Telavancin for the Treatment of Patients With Hospital-acquired Bacterial Pneumonia Caused by Staphylococcus aureus.

PURPOSE: Clinicians and stewardship programs are challenged with positioning of novel, higher priced antibiotic agents for the treatment of clinical infections. We developed a decision-analytic model to describe costs, including drug, total treatment costs, and health care outcomes, associated with telavancin (TLV) compared with vancomycin (VAN) for patients with Staphylococcus aureus (SA) hospital-acquired bacterial pneumonia (HABP). METHODS: This decision-analytic model assessed the treatment of SA-HABP with TLV versus VAN. Data were obtained from the ATTAIN (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia) clinical trials on the following: the probability of clinical cure; probability of nephrotoxicity; and prevalence of polymicrobial infection (30%), methicillin-resistant Staphylococcus aureus (MRSA) (68%), and SA with VAN MIC ≥1 µg/mL (85%). Data on length of stay for cure (10 days), failure (10 additional days), and nephrotoxicity (3.5 days) were based on literature. Cost per treated patient and incremental cost-effectiveness ratio (ICER) per additional cure were calculated for SA-HABP and for monomicrobial SA-HABP. One-way sensitivity analyses were performed. FINDINGS: Patients with SA-HABP were sub-grouped by methicillin susceptibility (n = 140, 32%) or resistance (n = 293, 68%), and occurrence of polymicrobial (n = 128, 30%) vs monomicrobial (n = 305, 70%) infections. Under the base case, hospital cost for patients with HABP treated with TLV was $42,564 and with VAN, it was $42,296. Telavancin was associated with higher drug ($2082) and nephrotoxicity ($467) costs and lower intensive care unit (-$1738) and ventilator (-$114) costs. ICER was $4156 per additional cure. ICER was sensitive to probabilities of cure, length of treatment in cures, intensive care unit cost, TLV cost, and additional length of stay due to failure. For monomicrobial SA-HABP, TLV was associated with a net cost savings of $907 per patient and yielded economic dominance. IMPLICATIONS: Our decision-analytic model suggests that TLV for monomicrobial SA-HABP is associated with higher drug acquisition costs but a favorable ICER relative to VAN, provided that effective antimicrobial stewardship limits therapy to 7 days. Sensitivity analyses suggest a potential economic benefit of TLV treatment with appropriate patient selection. Antimicrobial stewardship programs may be able to reduce total costs through judicious use of novel antimicrobial agents. ClinicalTrials.gov identifiers: NCT00107952 and NCT00124020.

Comparison of Linezolid and Vancomycin for Methicillin-Resistant Staphylococcus aureus Pneumonia: Institutional Implications.

OBJECTIVE: Recent studies suggesting clinical superiority of linezolid over vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia led to a change in our institution's clinical pathway/order form for hospital-acquired pneumonia, positioning linezolid as the preferred agent. Our objective was to assess the impact of this change within our institution. DESIGN: Retrospective electronic medical records review. METHODS: The analysis for this observational study included eligible patients admitted to our medical center between May 1, 2011, and August 31, 2014, with ICD-9 codes for MRSA and pneumonia. Included patients were at least 18 years of age and had vancomycin or linezolid initiated at least 2 days after admission and continued for at least 2 consecutive days. The primary end points were extent of antibiotic use before and after order form change and length of stay (LOS) and hospital charges in the two treatment groups. A secondary aim was to detect any gross discrepancies in patient outcomes such as treatment duration, mechanical ventilation duration, all-cause mortality rate, nephrotoxicity, and 30-day readmission between the two treatment groups. MEASUREMENTS AND MAIN RESULTS: Outcomes in 227 patients were assessed. Linezolid use increased 16.2% subsequent to the change in the order form. Although not statistically significant, the median hospital admission charge was $6200 lower in patients treated with linezolid compared with those treated with vancomycin ($25,900 vs $32,100). Hospital LOS was significantly associated with Charlson Comorbidity Index score (p<0.001), type of treatment (p=0.032), duration of treatment (p<0.001), mechanical ventilation (p<0.001), and intensive care unit admission (p<0.001). All-cause mortality favored linezolid treatment, and these patients were more likely to be discharged (shorter LOS). CONCLUSIONS: Although linezolid use increased markedly with this pathway/order form change, no negative institutional consequences or unfavorable patient outcomes were detected, justifying the change in policy from these perspectives.

Nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus treated with linezolid or vancomycin: A secondary economic analysis of resource use from a Spanish perspective.

OBJECTIVES: Adopting a unique Spanish perspective, this study aims to assess healthcare resource utilization (HCRU) and the costs of treating nosocomial pneumonia (NP) produced by methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized adults using linezolid or vancomycin. An evaluation is also made of the renal failure rate and related economic outcomes between study groups. DESIGN: An economic post hoc evaluation of a randomized, double-blind, multicenter phase 4 study was carried out. SCOPE: Nosocomial pneumonia due to MRSA in hospitalized adults. PARTICIPANTS: The modified intent to treat (mITT) population comprised 224 linezolid- and 224 vancomycin-treated patients. INTERVENTIONS: Costs and HCRU were evaluated between patients administered either linezolid or vancomycin, and between patients who developed renal failure and those who did not. PRIMARY ENDPOINTS: Analysis of HCRU outcomes and costs. RESULTS: Total costs were similar between the linezolid- (€17,782±€9,615) and vancomycin-treated patients (€17,423±€9,460) (P=.69). The renal failure rate was significantly lower in the linezolid-treated patients (4% vs. 15%; P<.001). The total costs tended to be higher in patients who developed renal failure (€19,626±€10,840 vs. €17,388±€9,369; P=.14). Among the patients who developed renal failure, HCRU (days on mechanical ventilation: 13.2±10.7 vs. 7.6±3.6 days; P=.21; ICU stay: 14.4±10.5 vs. 9.9±6.6 days; P=.30; hospital stay: 19.5±9.5 vs. 16.1±11.0 days; P=.26) and cost (€17,219±€8,792 vs. €20,263±€11,350; P=.51) tended to be lower in the linezolid- vs. vancomycin-treated patients. There were no statistically significant differences in costs per patient-day between cohorts after correcting for mortality (€1000 vs. €1,010; P=.98). CONCLUSIONS: From a Spanish perspective, there were no statistically significant differences in total costs between the linezolid and vancomycin pneumonia cohorts. The drug cost corresponding to linezolid was partially offset by fewer renal failure adverse events.

Estimating the cost-effectiveness of linezolid for the treatment of methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Taiwan.

BACKGROUND/PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) is associated with higher resource utilization, increased hospital stays, and mortality. We present a health economics model to understand the impact of using linezolid as the first-line treatment of MRSA NP in Taiwan. METHODS: We developed a cost-effectiveness model to estimate the costs and clinical outcomes of using linezolid 600 mg b.i.d. versus vancomycin 15 mg/kg b.i.d. as the first-line treatment of MRSA NP in Taiwan. The model is a decision-analytic analysis in which a MRSA-confirmed patient is simulated to utilize one of the treatments, using data from a clinical trial. Within each treatment arm, the patient can or cannot achieve clinical cure. Regardless of whether the clinical cure was achieved or not, the patient may or may not have experienced an adverse event. The per-protocol results for clinical cure were 57.6% and 46.6% for linezolid and vancomycin, respectively. RESULTS: The total cost of linezolid was $376 more per patient than that of vancomycin. Drug costs were higher for linezolid than for vancomycin ($1108 vs. $233), and hospitalization costs were lower ($4998 vs. $5496). With higher cost and higher cure rates for linezolid, the incremental cost per cure was $3421. CONCLUSION: This study projects linezolid to have higher drug costs, lower hospital costs, and higher overall costs compared with vancomycin. This is balanced against the higher clinical cure rate for linezolid. Depending on the willingness to pay for clinical cure, linezolid could be cost effective as the first-line treatment of NP in Taiwan.

Linezolid Versus Vancomycin in the Empiric Treatment of Nosocomial Pneumonia: A Cost-Utility Analysis Incorporating Results from the ZEPHyR Trial.

OBJECTIVE: To examine the cost-effectiveness of vancomycin versus linezolid in the empiric treatment of nosocomial pneumonias incorporating results from a recent prospective, double-blind, multicenter, controlled trial in adults with suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. METHODS: A decision-analytic model examining the cost-effectiveness of linezolid versus vancomycin for the empiric treatment of nosocomial pneumonia was created. Publicly available cost, efficacy, and utility data populated relevant model variables. A probabilistic sensitivity analysis varied parameters in 10,000 Monte-Carlo simulations, and univariate sensitivity analyses assessed the impact of model uncertainties and the robustness of our conclusions. RESULTS: Results indicated that the cost per quality-adjusted life-year (QALY) increased 6% ($22,594 vs. $23,860) by using linezolid versus vancomycin for nosocomial pneumonia. The incremental cost per QALY gained by using linezolid over vancomycin was $6,089, and the incremental cost per life saved was $68,615 with the use of linezolid. Vancomycin dominated linezolid in the subset of patients with documented MRSA. The incremental cost per QALY gained using linezolid if no mortality benefit exists between agents or a 60-day time horizon was analyzed was $19,608,688 and $443,662, respectively. CONCLUSIONS: Linezolid may be a cost-effective alternative to vancomycin in the empiric treatment of patients with suspected MRSA nosocomial pneumonia; however, results of our model were highly variable on a number of important variables and assumptions including mortality differences and time frame analyzed.

Managing skin and soft-tissue infection and nosocomial pneumonia caused by MRSA: a 2014 follow-up survey.

As a follow-up to our 2009 survey, in order to explore opinion and practice on the epidemiology and management of meticillin-resistant Staphylococcus aureus (MRSA) in Europe, we conducted a second survey to elicit current opinions on this topic, particularly around antibiotic choice, dose, duration and route of administration. We also aimed to further understand how the management of MRSA has evolved in Europe during the past 5 years. Members of an expert panel of infectious diseases specialists convened in London (UK) in January 2014 to identify and discuss key issues in the management of MRSA. Following this meeting, a survey was developed comprising 36 questions covering a wide range of topics on MRSA complicated skin and soft-tissue infection and nosocomial pneumonia management. The survey instrument, a web-based questionnaire, was sent to the International Society of Chemotherapy for distribution to registered European infection societies and their members. This article reports the survey results from the European respondents. At the time of the original survey, the epidemiology of MRSA varied significantly across Europe and there were differing views on best practice. The current findings suggest that the epidemiology of healthcare-associated MRSA in Europe is, if anything, even more polarised, whilst community-acquired MRSA has become much more common. However, there now appears to be a much greater knowledge of current treatment/management options, and antimicrobial stewardship has moved forward considerably in the 5 years since the last survey.

Modeling the economic impact of linezolid versus vancomycin in confirmed nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.

INTRODUCTION: We compared the economic impacts of linezolid and vancomycin for the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA)-confirmed nosocomial pneumonia. METHODS: We used a 4-week decision tree model incorporating published data and expert opinion on clinical parameters, resource use and costs (in 2012 US dollars), such as efficacy, mortality, serious adverse events, treatment duration and length of hospital stay. The results presented are from a US payer perspective. The base case first-line treatment duration for patients with MRSA-confirmed nosocomial pneumonia was 10 days. Clinical treatment success (used for the cost-effectiveness ratio) and failure due to lack of efficacy, serious adverse events or mortality were possible clinical outcomes that could impact costs. Cost of treatment and incremental cost-effectiveness per successfully treated patient were calculated for linezolid versus vancomycin. Univariate (one-way) and probabilistic sensitivity analyses were conducted. RESULTS: The model allowed us to calculate the total base case inpatient costs as $46,168 (linezolid) and $46,992 (vancomycin). The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with lower costs ($824 less) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA nosocomial pneumonia). Approximately 80% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). The results of our probabilistic sensitivity analysis indicated that linezolid is the cost-effective alternative under varying willingness to pay thresholds. CONCLUSION: These model results show that linezolid has a favorable incremental cost-effectiveness ratio compared to vancomycin for MRSA-confirmed nosocomial pneumonia, largely attributable to the higher clinical trial response rate of patients treated with linezolid. The higher drug acquisition cost of linezolid was offset by lower treatment failure-related costs and fewer days of hospitalization.

Health economic evaluation of patients treated for nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: secondary analysis of a multicenter randomized clinical trial of vancomycin and linezolid.

PURPOSE: Results from studies comparing health care resource use (HCRU), costs of treatment, and cost-effectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated. METHODS: We performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparator-controlled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-to-treat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental cost-effectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial. FINDINGS: Overall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly higher total costs. The point estimate incremental cost-effectiveness ratio for linezolid compared with vancomycin was $16,516 per treatment success, with linezolid dominant in 24% and dominated in <2% of bootstrapped samples. IMPLICATIONS: This phase 4 clinical trial conducted in patients with MRSA-confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycin-treated patients had similar HCRU and total overall costs. Fewer patients developed renal failure during the study while taking linezolid compared with vancomycin, and patients with a documented MSAE or renal failure had increased HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy in MRSA-confirmed nosocomial pneumonia.

European perspective and update on the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant hospital-acquired infections worldwide and remains a public health priority in Europe. Nosocomial pneumonia (NP) involving MRSA often affects patients in intensive care units with substantial morbidity, mortality and associated costs. A guideline-based approach to empirical treatment with an antibacterial agent active against MRSA can improve the outcome of patients with MRSA NP, including those with ventilator-associated pneumonia. New methods may allow more rapid or sensitive diagnosis of NP or microbiological confirmation in patients with MRSA NP, allowing early de-escalation of treatment once the pathogen is known. In Europe, available antibacterial agents for the treatment of MRSA NP include the glycopeptides (vancomycin and teicoplanin) and linezolid (available as an intravenous or oral treatment). Vancomycin has remained a standard of care in many European hospitals; however, there is evidence that it may be a suboptimal therapeutic option in critically ill patients with NP because of concerns about its limited intrapulmonary penetration, increased nephrotoxicity with higher doses, as well as the emergence of resistant strains that may result in increased clinical failure. Linezolid has demonstrated high penetration into the epithelial lining fluid of patients with ventilator-associated pneumonia and shown statistically superior clinical efficacy versus vancomycin in the treatment of MRSA NP in a phase IV, randomized, controlled study. This review focuses on the disease burden and clinical management of MRSA NP, and the use of linezolid after more than 10 years of clinical experience.

Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia.

Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of Staphylococcus aureus. We previously identified a monoclonal antibody (MAb) against AT that reduced disease severity in a mouse dermonecrosis model. Here, we evaluate the activity of an affinity-optimized variant, LC10, in a mouse model of S. aureus pneumonia. Passive immunization with LC10 increased survival and reduced bacterial numbers in the lungs and kidneys of infected mice and showed protection against diverse S. aureus clinical isolates. The lungs of S. aureus-infected mice exhibited bacterial pneumonia, including widespread inflammation, whereas the lungs of mice that received LC10 exhibited minimal inflammation and retained healthy architecture. Consistent with reduced immune cell infiltration, LC10-treated animals had significantly lower (P < 0.05) proinflammatory cytokine and chemokine levels in the bronchoalveolar lavage fluid than did those of the control animals. This reduction in inflammation and damage to the LC10-treated animals resulted in reduced vascular protein leakage and CO2 levels in the blood. LC10 was also assessed for its therapeutic activity in combination with vancomycin or linezolid. Treatment with a combination of LC10 and vancomycin or linezolid resulted in a significant increase (P < 0.05) in survival relative to the monotherapies and was deemed additive to synergistic by isobologram analysis. Consistent with improved survival, the lungs of animals treated with antibiotic plus LC10 exhibited less inflammatory tissue damage than those that received monotherapy. These data provide insight into the mechanisms of protection provided by AT inhibition and support AT as a promising target for immunoprophylaxis or adjunctive therapy against S. aureus pneumonia.

Pharmacotherapy for methicillin-resistant Staphylococcus aureus nosocomial pneumonia.

OBJECTIVE: To review the evidence for pharmacologic agents available in the treatment of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. DATA SOURCES: A search of PubMed (1975-July 2012) was conducted using a combination of the terms methicillin-resistant Staphylococcus aureus, pneumonia, nosocomial, vancomycin, linezolid, telavancin, ceftaroline, tigecycline, and quinupristin/dalfopristin. STUDY SELECTION AND DATA EXTRACTION: Randomized comparative clinical trials, meta-analyses, and review articles published in English were included. A manual review of the bibliographies of available literature was conducted and all relevant information was included. Observational and in vitro studies were incorporated as indicated. DATA SYNTHESIS: Pharmacotherapy for the treatment of nosocomial MRSA pneumonia is limited. Vancomycin has been the treatment of choice for several years. Linezolid has demonstrated similar efficacy to vancomycin in randomized clinical trials and recent data have suggested that it may be superior in some cases, although there are limitations to this conclusion. Telavancin has also demonstrated similar clinical efficacy to vancomycin; however, the drug is not commercially available in the US. Other agents with MRSA activity include ceftaroline, clindamycin, quinupristin/dalfopristin, and tigecycline, although the evidence for their use in nosocomial pneumonia is limited. CONCLUSIONS: Based on the currently available evidence and cost-effectiveness, vancomycin should continue to be the drug of choice for most patients with nosocomial MRSA pneumonia. Linezolid is a reasonable alternative for patients with treatment failure while receiving vancomycin, isolates with vancomycin minimum inhibitory concentrations over 2 µg/mL, allergic reactions, or vancomycin-induced nephrotoxicity.

[Effect of pharmacists' intervention on the antibiotic therapy for the methicillin-resistant Staphylococcus aureus (MRSA) infectious diseases in the intensive care unit].

Pharmacists are providing pharmaceutical care in general wards, but it is still not common in the intensive care unit (ICU). However, we have worked in ICU, and recommended the rational dosage regimen of the antibiotics to the physicians during the treatment period. Especially, the patients who were infected with methicillin-resistant Staphylococcus aureus (MRSA) in ICU should be provided appropriate antibiotic therapy, otherwise they have a poor prognosis. The aim of this study is to evaluate usefulness of the pharmacists' intervention on the antibiotic therapy for MRSA infectious diseases in the ICU. We investigated retrospectively the period of anti MRSA drugs administration, the medical cost, which includes cost of anti MRSA drugs and hospital charge, and the initial trough concentration of vancomycin (VCM). The patients with MRSA pneumonia were classified into two groups according to the pharmacists' intervention. The number of the patients who the pharmacists performed dosage regimen of anti MRSA drug was 11 (intervention group) and that of the patients who the pharmacists performed no intervention was 47 (control group). The average period of administration of anti MRSA drugs in the intervention group was significantly decreased in 5 days. Furthermore, if the pharmacists performed dosage regimen of anti MRSA drug to the patients in control group, the medical cost of 10 million yen would be saved. The initial trough concentrations of VCM were not significantly different between two groups. However, the achievement rates are 75.0% in intervention group and 66.7% in control group, if the goal of trough level of VCM is set from 5 to 15 µg/ml. Moreover, there are 75.0% in intervention group and 20.8% in control group, if the goal of trough level of VCM is set from 10 to 20 µg/ml, which is significantly different between the two groups. Therefore, it was suggested that the pharmacists in the ICU contributed to optimize the anti MRSA therapy and reduce the medical cost.

Clinical and economic outcomes for patients with health care-associated Staphylococcus aureus pneumonia.

While the increasing importance of methicillin-resistant Staphylococcus aureus (MRSA) as a pathogen in health care-associated S. aureus pneumonia has been documented widely, information on the clinical and economic consequences of such infections is limited. We retrospectively identified all patients admitted to a large U.S. urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 h of admission. Among these patients, those with suspected health care-associated pneumonia (HCAP) were identified using established criteria (e.g., recent hospitalization, admission from nursing home, or hemodialysis). Subjects were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) HCAP, based on initial S. aureus isolates. Initial therapy was designated "appropriate" versus "inappropriate" based on the expected susceptibility of the organism to the regimen received. We identified 142 patients with evidence of S. aureus HCAP. Their mean (standard deviation [SD]) age was 64.5 (17) years. Eighty-seven patients (61%) had initial cultures that were positive for MRSA. Most ( approximately 90%) patients received appropriate initial antibiotic therapy (86% for MRSA versus 91% for MSSA; P = 0.783). There were no significant differences between MRSA and MSSA HCAP patients in mortality (29% versus 20%, respectively), surgery for pneumonia (22% versus 20%), receipt of mechanical ventilation (60% versus 58%), or admission to the intensive care unit (79% versus 76%). Mean (SD) total charges per admission were universally high ($98,170 [$94,707] for MRSA versus $104,121 [$91,314]) for MSSA [P = 0.712]). Almost two-thirds of patients admitted to hospital with S. aureus HCAP have evidence of MRSA infection. S. aureus HCAP, irrespective of MRSA versus MSSA status, is associated with significant mortality and high health care costs, despite appropriate initial antibiotic therapy.

Identifying exposure targets for treatment of staphylococcal pneumonia with ceftobiprole.

Ceftobiprole is a cephalosporin with potent activity against methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). In order to treat patients with severe staphylococcal pneumonia, it is important to understand the drug exposure required to mediate the killing of multiple log(10) cells in a preclinical-infection model. We measured drug exposure in terms of the percentage of penetration of the drug into epithelial lining fluid (ELF) and in terms of the time for which the drug concentration was above the MIC (time>MIC) in plasma and ELF. In a murine model of staphylococcal pneumonia, we demonstrated that ceftobiprole penetrated into ELF from the plasma at a median level of nearly 69% (25th to 75th percentile range, 25 to 187%), as indexed to the ratio of values for the area under the concentration-time curve in ELF and plasma. The total-drug times>MIC in ELF that were required to kill 1 log(10) and 2 log(10) CFU/g of lung tissue were 15% and 25% of the dosing interval. We also examined the penetration of ELF by ceftobiprole in volunteers, demonstrating mean and median penetration percentages of 25.5% and 15.3%, respectively (25th to 75th percentile range, 8 to 30%). Attainment rates were calculated for kill targets of 1 log(10) and 2 log(10) CFU/g, taken from the murine model, but using the volunteer ceftobiprole ELF penetration data. The standard dose for ceftobiprole is 0.5 g every 8 h as a 2-h infusion. The attainment rates remained above 90% for 1-log(10) and 2-log(10) CFU/g kill targets at MICs of 1 and 0.5 mg/liter, respectively. Taking the expectation over the distribution of ceftobiprole MICs for 4,958 MRSA isolates showed an overall target attainment of 85.6% for a 1-log(10) CFU/g kill and 79.7% for a 2-log(10) CFU/g kill. It is important to derive exposure targets in preclinical-infection models of the infection site so that these targets can be explored in clinical trials in order to optimize the probability of a good clinical outcome.

Cost-effectiveness of linezolid vs vancomycin in suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany.

BACKGROUND: The oxazolidinone antibiotic linezolid has demonstrated efficacy in treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In a retrospective analysis of two prospective randomized clinical trials in patients with nosocomial pneumonia (NP), initial therapy with linezolid produced significantly better clinical cure and survival rates than vancomycin in the subset of patients with documented MRSA infection. This study was designed to evaluate the economic impact of these clinical outcomes from the perspective of the German health care system to determine the use of these regimens in the light of limited resources and rising costs. METHODS: A decision-analytic model using clinical trial data was developed to examine the costs and outcomes of treatment with linezolid or vancomycin in hospitalized patients with NP caused by suspected MRSA. The model followed an average patient from initiation of empiric treatment until treatment success, death, or second-line treatment failure. Local treatment patterns and resource use were obtained from a Delphi panel. Costs were taken from published sources. Outcomes included total cost per patient, cost per additional cure, cost per death avoided, and cost per life-year gained. RESULTS: The model calculated that linezolid was associated with an 8.7% higher cure rate compared with vancomycin (73.6% vs 64.9%, respectively). Average total costs per episode for linezolid- and vancomycin-treated patients were 12,829 and 12,409, respectively. Death rates were 13.2% lower with linezolid than with vancomycin (20.7% vs 33.9%), resulting in an average of 2.3 life-years gained per linezolid-treated patient in a 65-year-old cohort (14.0 life-years vs 11.7 life-years). With linezolid, incremental costs per death avoided and per patient cured were 3,171 and 4,813, respectively. The base case estimated a similar mean length of stay for both drugs (11.2 vs 10.8 days). One-way sensitivity analyses did not change the overall results. CONCLUSION: The model estimated a higher clinical cure (+8.7%) and survival (+13.2%) for linezolid compared with vancomycin at an incremental cost of 420 per treatment episode. The cost-benefit profile suggests that linezolid could be considered a cost-effective alternative to vancomycin in the treatment of patients with NP caused by suspected MRSA in Germany.

Telavancin penetration into human epithelial lining fluid determined by population pharmacokinetic modeling and Monte Carlo simulation.

Telavancin is an investigational bactericidal lipoglycopeptide with a multifunctional mechanism of action, as demonstrated against methicillin-resistant Staphylococcus aureus. While the plasma pharmacokinetics have been described, the extent of the penetration of the drug into the lung, measured by the epithelial lining fluid (ELF), remains unknown. Population modeling and Monte Carlo simulation were employed to estimate the penetration of telavancin into ELF. Plasma and ELF pharmacokinetic data were obtained from 20 healthy volunteers, and the pharmacokinetic samples were assayed by a validated liquid chromatography-tandem mass spectrometry technique. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer. The model parameters were identified in a population pharmacokinetic analysis (BigNPAG). Monte Carlo simulation of 9,999 subjects was performed to calculate the ELF/plasma penetration ratios by estimating the area under the concentration-time curve (AUC) for the drug in ELF (AUC(ELF)) and for the free drug in plasma (free AUC(plasma)) from zero to infinity after a single dose. After the Bayesian step, the overall fits of the model to the data were good, and plots of predicted versus observed concentrations in plasma and ELF showed slopes and intercepts very close to the ideal values of 1.0 and 0.0, respectively. The median AUC(ELF)/free AUC(plasma) penetration ratio was 0.73, and the 25th and 75th percentile value ratios were 0.43 and 1.24, respectively. In uninfected lung tissue, the median AUC(ELF) is approximately 75% of the free AUC(plasma).