Recombinant production of Trx-Ib-AMP4 and Trx-E50-52 antimicrobial peptides and antimicrobial synergistic assessment on the treatment of methicillin-resistant Staphylococcus aureus under in vitro and in vivo situations.

PURPOSE: The production of alternative novel antimicrobial agents is considered an efficient way to cope with multidrug resistance among pathogenic bacteria. E50-52 and Ib-AMP4 antimicrobial peptides (AMPs) have illustrated great proven antibacterial effects. The aim of this study was recombinant production of these AMPs and investigation of their synergistic effects on methicillin-resistant Staphylococcus aureus (MRSA). METHOD: At first, the codon optimized sequences of the Ib-AMP4 (UniProt: 024006 (PRO_0000020721), and E50-52 (UniProtKB: P85148) were individually ligated into the pET-32α vector and transformed into E. coli. After the optimization of production and purification steps, the MIC (Minimum inhibitory concentration), time kill and growth kinetic tests of recombinant proteins were determined against MRSA. Finally, the in vivo wound healing efficiency was tested. RESULTS AND CONCLUSION: The recorded MIC of recombinant Trx-Ib-AMP4, Trx-E50-52 against MRSA bacterium were 0.375 and 0.0875 mg/mL respectively. The combination application of the produced AMPs by the checkerboard method confirmed their synergic activity. The results of the time-kill showed sharply decrease of the number of viable cells with over five time reductions in log10 CFU/mL by the combination of Trx-E50-52 and Trx-IbAMP4 at 2 × MIC within 240 min. The growth kinetic results confirmed the combination of Trx-E50-52 and Trx-IbAMP4 had much greater success in the reduction of over 50 % of MRSA suspensions' turbidity within the first hour. Wound healing assay and histological analysis of infected mice treated with Trx-Ib-AMP4 or Trx-E50-52 compared with those treated with a combination of Trx-Ib-AMP4 and Trx-E50-52 showed significant synergic effects.

Antibiotic use among twelve Canadian First Nations communities: a retrospective chart review of skin and soft tissue infections.

BACKGROUND: Previous publications indicated an emerging issue with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), particularly skin and soft tissue infections (SSTIs), in Indigenous communities in Canada. The objectives of this analysis were to explore the prevalence of SSTIs due to CA-MRSA and patterns of antimicrobial use in the community setting. METHODS: A retrospective chart review was conducted as part of an environmental scan to assess antibiotic prescriptions in 12 First Nations communities across five provinces in Canada including Alberta, Saskatchewan, Manitoba, Ontario, and Québec. Charts were randomly selected from nursing stations and patients who had accessed care in the previous 12 months and were ≥ 18 years were included in the review. Data was collected from September to December, 2013 on antibiotic prescriptions, including SSTIs, clinical symptoms, diagnostic information including presence of CA-MRSA infection, and treatment. RESULTS: A total of 372 charts were reviewed, 60 from Alberta, 70 from Saskatchewan, 120 from Manitoba, 100 from Ontario, and 22 from Québec. Among 372 patients, 224 (60.2%) patients had at least one antibiotic prescription in the previous 12 months and 569 prescriptions were written in total. The prevalence of SSTIs was estimated at 36.8% (137 cases of SSTIs in 372 charts reviewed). In 137 cases of SSTIs, 34 (24.8%) were purulent infections, and 55 (40.2%) were due to CA-MRSA. CONCLUSIONS: This study has identified a high prevalence of antibiotic use and SSTIs due to CA-MRSA in remote and isolated Indigenous communities across Canada. This population is currently hard to reach and under-represented in standard surveillance system and randomized retrospective chart reviews can offer complimentary methodology for monitoring disease burden, treatment and prevention.

Dalbavancin in the treatment of different gram-positive infections: a real-life experience.

Dalbavancin is a lipoglycopeptide with a very prolonged half-life enabling treatment with a single intravenous administration that has been approved to treat complicated skin and soft-tissue infections. Information on the efficacy and safety of dalbavancin in other situations is very scarce. This retrospective study included adult patients who received at least one dose of dalbavancin between 2016 and 2017 in 29 institutions in Spain. The primary objective was to report the use of dalbavancin in clinical practice, including its efficacy and tolerability. The potential impact of dalbavancin on reducing the length of hospital stay and hospital costs was also evaluated. A total of 69 patients received dalbavancin during the study period (58.0% male; median age 63.5 years). Dalbavancin was used to treat prosthetic joint infection (29.0%), acute bacterial skin and skin-structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly caused by Staphylococcus aureus (27 isolates), coagulase-negative staphylococci (24 isolates) and Enterococcus spp. (11 isolates). All but two patients received previous antibiotics for a median of 18 days. Dalbavancin was administered for a median of 21 days (range 7-168 days), and concomitant antimicrobial therapy was prescribed to 25 patients (36.2%). The overall clinical success rate of dalbavancin was 84.1%. Adverse events, mainly mild in intensity, were reported in nine patients. Overall, dalbavancin was estimated to reduce hospitalisation by 1160 days, with an estimated overall cost reduction of €211 481 (€3064 per patient). Dalbavancin appears to be an effective therapy for many serious Gram-positive infections.

Pharmacokinetic and Pharmacodynamic Analyses To Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Patients with Serious Infections Caused by Gram-Positive Pathogens.

Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection model studies suggest that the pharmacokinetic/pharmacodynamic (PK/PD) drivers for efficacy are area under the concentration-time curve from 0 to 24 h at steady state (AUC0-24ss), AUC/MIC, and time above the MIC during the dosing interval (T > MIC), while QTc prolongation was associated with the maximal concentration at steady state (Cmaxss) in a thorough QTc phase 1 study. Using PK data collected from 470 patients from the previously conducted phase 3 complicated skin and skin structure infection (cSSSI) trials, population PK modeling and Monte Carlo simulation (MCS) were used to identify a fixed iclaprim dosage regimen for the ongoing phase 3 ABSSSI studies that maximizes AUC0-24ss, AUC/MIC, and T > MIC while minimizing the probability of a Cmaxss of ≥800 ng/ml relative to the values for the previously employed cSSSI regimen of 0.8 mg/kg of body weight infused intravenously over 0.5 h every 12 h. The MCS analyses indicated that administration of 80 mg as a 2-h infusion every 12 h provides 28%, 28%, and 32% increases in AUC0-24ss, AUC/MIC, and T > MIC, respectively, compared to values for the 0.8-mg/kg cSSSI regimen, while decreasing the probability of a Cmaxss of ≥800 ng/ml, by 9%. Based on PK/PD analyses, 80 mg iclaprim administered over 2 h every 12 h was selected as the dosing scheme for subsequent phase 3 clinical trials.

Assessment of telavancin minimal inhibitory concentrations by revised broth microdilution method in phase 3 complicated skin and skin-structure infection clinical trial isolates.

The broth microdilution (BMD) MIC testing method for telavancin was recently revised BMD (rBMD) to improve accuracy and reproducibility. Staphylococcus aureus isolates from telavancin phase 3 complicated skin and skin-structure infection (cSSSI) studies were tested using the rBMD method. Retesting of 1132 isolates produced MICs ranging from ≤0.015 to 0.12µg/mL that were 8-fold lower than the original method. All isolates tested remained susceptible to telavancin at the revised susceptibility breakpoint of 0.12µg/mL. The clinical cure and microbiological eradication rates were 90% (368/409) and 89% (366/409) for telavancin-treated patients, and were similar for patients with methicillin-susceptible and -resistant S. aureus isolates and S. aureus isolates with elevated vancomycin MICs (≥1µg/mL). The data presented here are aimed to update the literature and better inform clinicians and clinical microbiologists about the revised telavancin MICs, as well as the corresponding clinical and microbiological cure rates for cSSSI patients.

Use of Oritavancin in Moderate-to-Severe ABSSSI Patients Requiring IV Antibiotics: A U.S. Payer Budget Impact Analysis.

BACKGROUND: It is estimated that acute bacterial skin and skin structure infections (ABSSSI) account for nearly 10% of hospital admissions and 3.4-3.8 million emergency department visits per year in the United States. Analyses of hospital discharge records indicate 74% of ABSSSI admissions involve empiric treatment with methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics. Analysis has shown that payer costs could be reduced if moderate-to-severe ABSSSI patients were treated to a greater extent in the observational unit followed by discharge to outpatient parenteral antibiotic therapy (OPAT). Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against gram-positive bacteria, including MRSA. OBJECTIVE: To estimate the impact on a U.S. payer's budget of using single-dose oritavancin in ABSSSI patients with suspected MRSA involvement who are indicated for intravenous antibiotics. METHODS: A decision analytic model based on current clinical practice was developed to estimate the economic value of decreased hospital resource consumption by using single-dose oritavancin over a 1-year time horizon. Use of antibiotics was informed by an analysis of the Premier Research Database. Demographic and clinical data were derived from a targeted literature review. Emergency department, observation, laboratory, and administration costs used were Medicare National Limitation amounts. Drug costs were 2014 wholesale acquisition costs. RESULTS: For a hypothetical U.S. payer with 1,000,000 members, it is expected that approximately 14,285 members per year will be diagnosed with ABSSSI severe enough to indicate intravenous antibiotics with MRSA activity. Based on this simulation, use of single-dose oritavancin in 26% of these patients was estimated to reduce the number of inpatient admissions, reduce length of stay for patients requiring admission, and reduce the number of days a patient needs to receive daily infusions in the OPAT clinic. The total patient days decreased from 171,125 to 133,435 with a total annual budget impact of -$12,550,000 or -$1.05 per member per month (PMPM). Total inpatient and outpatient costs were reduced by $9,970,000 (19.7%) and $2,580,000 (4.2%), respectively. Inpatient cost savings were derived from a reduction in admissions, length of stay, and lower drug administration burden. Outpatient costs were reduced by lower drug administration burden in the OPAT setting. A sensitivity analysis demonstrated that the model was most sensitive to population estimates. CONCLUSIONS: Use of single-dose oritavancin in moderate-to-severe ABSSSI patients, including those with suspected MRSA, was projected to deliver an estimated cost reduction to U.S. payers of $1.05 PMPM by avoiding hospitalization in appropriate patients and reducing outpatient costs associated with multiday parenteral antibiotic therapy. DISCLOSURES: This work was funded by The Medicines Company. Jensen, Wu, and Cyr are employees of ICON Health Economics, which provides consulting services to the biopharmaceutical industry, including The Medicines Company. Fan and Sulman are employees and shareholders of The Medicines Company. Dufour and Lodise have provided consulting services to The Medicines Company. Nicolau provided model input but did not receive an honorarium for contributions on this project. Nicolau is a speaker for The Medicines Company. Study concept and design were contributed by Jensen and Wu, along with the other authors. Jensen, Wu, Fan, and Sulham collected the data, with assistance from Cyr. Data interpretation was performed by Sulham, Jensen, Wu, and Fan, assisted by Lodise, Nicolau, and Dufour. The manuscript was written by Jensen, Wu, and Sulham, with assistance from Cyr, and revised by Lodise, Nicolau, and Dufour, with assistance from the other authors.

MRSA in Croatia: prevalence and management.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with increased morbidity, mortality and length of hospital stay. MRSA is a major pathogen in hospitals and an important pathogen in community infections with few severe and fatal cases. However, MRSA causes the majority of skin and soft tissue infections in the US. The burden of community MRSA is much smaller in Europe, but there are reports of livestock-associated MRSA (LA-MRSA) isolated from pigs and cattle causing significant infections in the people who are connected to these farms. MRSA has been present in Croatia for more than 45 years, and it exerts a different impact on health-care infections. A remarkable increase in MRSA percentage was noted in primarily sterile samples in 2002 (37%) in comparison to 2001 (31%). This percentage remained quite high until 2008, when the first signs of a reduced trend were observed. The lowest percentage was 22% in 2012.

Assessing the economic value of avoiding hospital admissions by shifting the management of gram+ acute bacterial skin and skin-structure infections to an outpatient care setting.

OBJECTIVE: To estimate, from a US payer perspective, the cost offsets of treating gram positive acute bacterial skin and skin-structure infections (ABSSSI) with varied hospital length of stay (LOS) followed by outpatient care, as well as the cost implications of avoiding hospital admission. METHODS: Economic drivers of care were estimated using a literature-based economic model incorporating inpatient and outpatient components. The model incorporated equal efficacy, adverse events (AE), resource use, and costs from literature. Costs of once- and twice-daily outpatient infusions to achieve a 14-day treatment were analyzed. Sensitivity analyses were performed. Costs were adjusted to 2015 US$. RESULTS: Total non-drug medical cost for treatment of ABSSSI entirely in the outpatient setting to avoid hospital admission was the lowest among all scenarios and ranged from $4039-$4924. Total non-drug cost for ABSSSI treated in the inpatient setting ranged from $9813 (3 days LOS) to $18,014 (7 days LOS). Inpatient vs outpatient cost breakdown was: 3 days inpatient ($6657)/11 days outpatient ($3156-$3877); 7 days inpatient ($15,017)/7 days outpatient ($2495-$2997). Sensitivity analyses revealed a key outpatient cost driver to be peripherally inserted central catheter (PICC) costs (average per patient cost of $873 for placement and $205 for complications). LIMITATIONS: Drug and indirect costs were excluded and resource use was not differentiated by ABSSSI type. It was assumed that successful ABSSSI treatment takes up to 14 days per the product labels, and that once-daily and twice-daily antibiotics have equal efficacy. CONCLUSION: Shifting ABSSSI care to outpatient settings may result in medical cost savings greater than 53%. Typical outpatient scenarios represent 14-37% of total medical cost, with PICC accounting for 28-43% of the outpatient burden. The value of new ABSSSI therapies will be driven by eliminating the need for PICC line, reducing length of stay and the ability to completely avoid a hospital stay.

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.

Antibiotic treatment patterns across Europe in patients with complicated skin and soft-tissue infections due to meticillin-resistant Staphylococcus aureus: a plea for implementation of early switch and early discharge criteria.

This retrospective observational medical chart review aimed to describe country-specific variations across Europe in real-world meticillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI) treatment patterns, antibiotic stewardship activity, and potential opportunities for early switch (ES) from intravenous (i.v.) to oral formulations and early discharge (ED) from hospital using standardised data collection and criteria and economic implications of these opportunities. Patients were randomly sampled from 12 countries (Austria, Czech Republic, France, Germany, Greece, Ireland, Italy, Poland, Portugal, Slovakia, Spain and the UK), aged ≥18 years, with documented MRSA cSSTI, hospitalised between 1 July 2010 and 30 June 2011, discharged alive by 31 July 2011. Of 1502 patients, 1468 received MRSA-targeted therapy. Intravenous-to-oral switch rates ranged from 2.0% to 20.2%, i.v. length of therapy from 10.1 to 18.6 days and hospital length of stay (LoS) from 15.2 to 25.0 days across Europe. Of 341 sites, 82.9% had antibiotic steering committees, 23.7% had i.v.-to-oral switch antibiotic protocols and 12.9% had ED protocols for MRSA cSSTI. ES and ED eligibility ranged from 12.0% (Slovakia) to 56.3% (Greece) and from 10% (Slovakia) to 48.2% (Portugal), respectively. Potential cost savings per ED-eligible patient ranged from €414 (Slovakia) to €2703 (France). MRSA cSSTI treatment patterns varied widely across countries, but further reductions in i.v. therapy, hospital LoS and associated costs could be realised. These data provide insight into clinical practice patterns across diverse European healthcare systems and identify potential opportunities for local clinicians and policy-makers to improve clinical care and cost-effectiveness of this therapeutic area.

Economic evaluation of treatment for MRSA complicated skin and soft tissue infections in Glasgow hospitals.

In the UK, methicillin-resistant Staphylococcus aureus (MRSA)-associated skin and soft tissue infections (SSTIs) are predominantly managed in the hospital using intravenous (IV) glycopeptides. We set out to explore the potential for and relative healthcare costs of earlier hospital discharge through switch to oral antibiotic therapy (linezolid or rifampicin and doxycycline) or continuation of IV therapy (teicoplanin) via an outpatient parenteral antimicrobial therapy (OPAT) service. Over 16 months, 173 patients were retrospectively identified with MRSA SSTI, of whom 82.8 % were treated with IV therapy. Thirty-seven patients were potentially suitable for earlier discharge with outpatient therapy. The model assumed 3 days of inpatient management and a maximum of 14 days of outpatient therapy. For the status quo, where patients received only inpatient care with IV therapy, hospital costs were calculated at £12,316 per patient, with 97 % of costs accounted for by direct bed day costs. The mean total cost savings achievable through OPAT or oral therapy was estimated to be £6,136 and £6,159 per patient treated, respectively. A significant proportion of patients with MRSA SSTI may be suitable for outpatient management with either oral therapy or via OPAT, with the potential for significant reduction in healthcare costs.

Using daptomycin in hospitalised patients with cSSTI caused by Staphylococcus aureus has an impact on costs.

BACKGROUND: The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK. METHODS: A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews. RESULTS: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation. CONCLUSIONS: This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs.

Cost-effectiveness of linezolid in methicillin-resistant Staphylococcus aureus skin and skin structure infections.

Linezolid is a novel oxazolidinone antibacterial agent with a broad clinical application, especially in methicillin-resistant Staphylococcus aureus skin and soft-tissue infections and skin and skin-structure infections. Pharmacoeconomic advantages include decreased hospital duration, reduction in intravenous antibiotic use and early discharge opportunities that contribute to an overall reduction in healthcare resources. Linezolid's oral formulation has a pharmacokinetic profile that is similar to its intravenous formulation, which creates opportunities for early discharge not available to comparators like vancomycin and daptomycin. Both vancomycin and daptomycin require intravenous therapy, which compounds the resources required in treating methicillin-resistant S. aureus skin and soft tissue/skin and skin structure infections. Pharmacoeconomic studies have demonstrated an overall reduction in total direct costs to the payer in favor of linezolid over its comparators. Its overall reduction in healthcare utilization makes it an appropriate alternative to the standard therapy, vancomycin.

Comparing the use of intravenous antibiotics under the medical benefit with the use of oral antibiotics under the pharmacy benefit in treating skin and soft tissue infections.

PURPOSE: To assess differences in the simultaneous management of pharmacy and medical benefits by analyzing the health care utilization and costs associated with managed care patients who received oral linezolid as a pharmacy benefit or intravenous (IV) daptomycin or IV vancomycin as medical benefits for skin and soft tissue infections (SSTIs). METHODOLOGY: The first medical or pharmacy claim from 03/01/2007 to 03/01/2010 was defined as the index date. Patients 18-64 years of age, with an inpatient SSTI diagnosis and > or = 1 target antibiotic claim(s), were included. Follow-up was 45 days; hospitalizations, emergency room (ER) visits, outpatient medical services, prescription fills, and total health care costs were compared for the treatments using univariate generalized linear modeling (GLM) analyses. Total health care costs were compared with GLM multivariate analyses adjusting for baseline covariate values. RESULTS: Of the 8,905 patients included, 2,123 received linezolid, 5,503 vancomycin, and 1,279 daptomycin therapy; 14.4% of linezolid, 37.7% of vancomycin, and 22.8% of daptomycin patients were re-hospitalized (p < 0.001). A smaller proportion of linezolid patients (8.6%) required emergency services, versus 11.6% of vancomycin and 10.8% of daptomycin patients (p < 0.001). Multivariate analyses showed vancomycin costs to be significantly lower than daptomycin costs, -$5,425 (95% CI, -$1,535 to -$9,315), and a significantly higher mean cost difference for vancomycin, $11,182 (95% CI, $6,255 to $16,108), and daptomycin, $16,607 (95% CI, $9,426 to $23,788), versus linezolid. CONCLUSION: Patients treated with oral linezolid had fewer re-hospitalizations and emergency room visits and lower total costs compared with patients who received vancomycin or daptomycin therapy, suggesting that oral linezolid, which is covered under members' pharmacy benefits, may be more cost-effective than the two intravenous treatments for SSTIs.

Cost avoidance using linezolid for methicillin-resistant Staphylococcus aureus infections in a specialist diabetes foot clinic.

OBJECTIVES: An audit was performed to determine whether linezolid (Zyvox, Pharmacia Limited, Sandwich, UK) was being used in accordance with local guidelines and if this had an effect on admissions for diabetes foot ulceration. METHODS: Seven hundred and four patient records from 2005 to 2010 in the Diabetes Foot Clinic, Royal Infirmary of Edinburgh were audited for methicillin-resistant Staphylococcus aureus (MRSA) infections, admissions and antibiotic use. RESULTS: Seventeen percent (n = 119) of patients had proven MRSA infections. Of these, 28% (n = 33) were prescribed linezolid, 94% (n = 31) for up to 14 days and none for >28 days. Eight (24%) had repeated courses. Ninety-one percent (n = 30) either avoided admission or were discharged early with resolution of infection. Four out of 33 patients had reversible blood abnormalities. The total cost for linezolid over this period was £58 000. However, 420 bed days, costing £500/day, were avoided, producing a total saving of £210 000 on inpatient costs. CONCLUSIONS: Linezolid guidelines reduced lengths of stay, inpatient costs and overuse of this expensive but effective treatment.

MRSA eradication in dermatologic outpatients - theory and practice.

BACKGROUND: The dissemination of methicillin resistant staphylococcus aureus (MRSA) is an increasing challenge in medical care. Apart from hospital acquired MRSA, there has also been an increase in community acquired and livestock associated MRSA. While the risks of MRSA (e. g. wound infections) and consequences (e. g. rejection of patients) are well known, there are little data on the effectiveness of eradication procedures. PATIENTS AND METHODS: 32 patients with proven MRSA colonization were monitored during eradication for the following aspects: (1) localization of MRSA (swabs from hairline, anterior nares, throat, axillae, groins, perineum, and wounds, if present), (2) presence of eradication-impairing factors, (3) length of time needed for eradication, (4) cost of eradication, (5) molecular fingerprint and risk assessment (spa-types). RESULTS: We describe the successful eradication of MRSA in all 32 patients. Most positive nasal swabs were obtained from the anterior nares and the throat and only rarely from the hairline or axillae. The greater the number of positive swabs, the more time was needed for eradication. In most patients (37.5%), eradication with topical antiseptics was successful. The average time for eradication was 12.97 (± 7.6) days. Twelve patients required systemic antibiotic therapy. Treatment costs associated with the use of systemic antibiotics were significantly higher. The most frequent spa types were t032 and t003. CONCLUSIONS: We report successful MRSA eradication in outpatients. Systemic antibiotics are unnecessary in the majority of patients. A combined anti-MRSA strategy for inpatients and outpatients is recommended.

Cost-effectiveness analysis of linezolid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus: complicated skin and skin structure infection using Bayesian methods for evidence synthesis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and skin structure infection (cSSSI) is a prominent infection encountered in hospital and outpatient settings that is associated with high resource use for the health-care system. OBJECTIVE: A decision analytic (DA) model was developed to evaluate the cost-effectiveness analysis (CEA) of linezolid, daptomycin, and vancomycin in MRSA cSSSI. METHODS: Bayesian methods for evidence synthesis were used to generate efficacy and safety parameters for a DA model using published clinical trials. CEA was done from the US health-care perspective. Efficacy was defined as a successfully treated patient at the test of cure without any adverse reaction. Primary outcome was the incremental cost-effectiveness ratio between linezolid and vancomycin, daptomycin and vancomycin, and linezolid and daptomycin in MRSA cSSSI. Univariate and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS: The total direct costs of linezolid, daptomycin, and vancomycin were $18,057, $20,698, and $23,671, respectively. The cost-effectiveness ratios for linezolid, daptomycin, and vancomycin were $37,604, $44,086, and $52,663 per successfully treated patient, respectively. Linezolid and daptomycin were dominant strategies compared to vancomycin. However, linezolid was dominant when compared to daptomycin. The model was sensitive to the duration of daptomycin and linezolid treatment. CONCLUSION: Linezolid and daptomycin are potentially cost-effective based on the assumptions of the DA model; however, linezolid appears to be more cost-effective compared to daptomycin and vancomycin for MRSA cSSSIs.