Outcomes and metrics for antimicrobial stewardship: survey of physicians and pharmacists.

We conducted a survey to compare antimicrobial stewardship outcomes considered to be most important with those used in practice as metrics. Respondent opinion of important outcomes compared with those collected as metrics were antimicrobial use (15% vs 73%), antimicrobial cost (10% vs 73%), appropriateness of antimicrobial use (56% vs 51%), infection-related mortality rate (34% vs 7%), and antibiotic-associated length of stay (22% vs 12%). Patient outcomes are important to many practitioners but are rarely used as metrics.

Breaking down the barriers: challenges with development and implementation of an industry-sponsored antimicrobial stewardship data collection and analysis tool.

Partnership between clinicians and the pharmaceutical industry with a focus on antimicrobial stewardship research initiatives is a necessary step toward meeting the shared goals of combating inappropriate antimicrobial use, improving patient outcomes, and minimizing resistance development. Achieving these goals requires outcomes-focused data collection and monitoring tools for antimicrobial stewardship programs (ASP) that consider real-world data about how antimicrobials are used to treat patients. Here we highlight the experiences and challenges associated with the development and implementation of an industry-sponsored electronic antimicrobial stewardship data collection and analysis tool (AS-DCAT). The benefits and risks of the industry-sponsored AS-DCAT from the perspectives of the sponsoring company and participating sites are discussed. Barriers encountered as well as general considerations and recommendations for preventing or overcoming those barriers for future studies and tool development are provided.

Optimizing delivery of care for patients with MRSA infection: focus on transitions of care.

Staphylococcus aureus is among the most prevalent pathogens isolated from hospitalized patients; those infected with methicillin-resistant strains have longer hospital stays and higher total costs compared with those infected by methicillin-susceptible strains. A multidisciplinary team of health care providers, including hospitalists and other hospital-based physicians, clinical pharmacists, infectious disease specialists, infection control professionals, and case managers, is key to improving treatment and outcomes in these patients. Optimizing transitions of care for hospitalized patients with S aureus infections can improve quality and reduce total costs of care. Hospital length of stay can be shortened by initiating timely, appropriate empiric therapy and by transitioning suitable patients to outpatient antimicrobial therapy. The number of hospitalizations can be reduced by identifying patients who are suitable candidates for initial outpatient antimicrobial therapy. Consistent with good antimicrobial stewardship, the risk of resistance can be minimized by de-escalating empiric therapy to a more narrow-spectrum agent once culture and susceptibility testing results are known. There are several antimicrobial agents available for the management of S aureus infections, including methicillin-resistant S aureus. Consideration of these agents' characteristics may facilitate optimal transition of patients through health care settings.

Clinical, microbiologic, and genetic determinants of persistent methicillin-resistant Staphylococcus aureus bacteremia.

Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) often persists despite full susceptibility to vancomycin; therefore, associated factors were assessed. A retrospective cohort analysis of 222 patients with MRSAB treated with vancomycin was conducted; patients with persistent MRSAB (pMRSAB) were compared to those with nonpersistent bacteremia (NPB). Incidence of pMRSAB was 9%. More patients with vancomycin MIC = 2 mg/L had pMRSAB (16%) compared to patients with vancomycin MIC <2 mg/L (5%), P = 0.012. SCCmec type and Panton-Valentine leukocidin production were similar between patients with pMRSAB and NPB. There was no difference in vancomycin troughs, time to first dose, or area under the concentration-time curve/MIC between groups. More metastatic complications were observed in pMRSAB 63% versus NPB 32% (P = 0.005). Multivariate analysis found endocarditis (odds ratio [OR], 2.3; P = 0.021), complicated MRSAB (OR, 2.6; P = 0.009), vancomycin MIC = 2 (OR, 2.6; P = 0.009), and septic shock (OR 2.2 P = 0.031), which were independent predictors of pMRSAB.

Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients.

STUDY OBJECTIVE: To describe the characteristics and clinical outcomes of hematopoietic stem cell transplant (HSCT) recipients who received adjunctive cytomegalovirus intravenous immune globulin (CMV-IVIG) for probable or proven CMV disease. DESIGN: Retrospective cohort study. SETTING: Large, university-affiliated, tertiary-care medical center. PATIENTS: Thirty-five adult HSCT recipients who received at least one dose of CMV-IVIG for adjunctive treatment of probable or proven CMV disease between January 1, 1999, and December 31, 2007. MEASUREMENTS AND MAIN RESULTS: All-cause mortality at hospital discharge was the primary outcome. All patients received an allogeneic HSCT. Twenty-six patients (74%) had pneumonitis, nine (26%) had enteritis, and 29 (83%) had CMV viremia. All patients received concomitant antiviral therapy; 31 (89%) received ganciclovir, and 14 (40%) received foscarnet. All-cause mortality at hospital discharge was 49% (17 patients). Patient characteristics associated with mortality included requiring intubation for CMV pneumonia (11 [79%] of 14 nonsurvivors vs 3 (25%) of 12 survivors, p=0.016) and earlier disease onset after HSCT (median 48 days for nonsurvivors vs 106 days for survivors, p<0.001). In the multivariate analysis, only requiring intubation for CMV pneumonia remained a significant risk factor for increased mortality. A low rate of adverse events was attributed to CMV-IVIG, with mild hypertension (two patients [6%]) and erythema and chills (one patient [3%]) being the most common. CONCLUSION: The mortality rate in our study population was similar to previous reports in the literature and may be somewhat lower than rates reported with antiviral monotherapy. Our analysis suggests that factors associated with mortality include the need for intubation and, possibly, earlier onset of CMV disease after HSCT. Treatment with CMV-IVIG appears to be well tolerated in HSCT recipients. These findings support further trials of CMV-IVIG efficacy in this setting.

Assessment of an alternative meropenem dosing strategy compared with imipenem-cilastatin or traditional meropenem dosing after cefepime failure or intolerance in adults with neutropenic fever.

STUDY OBJECTIVE: To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem-cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia. DESIGN: Retrospective, single-center cohort study. SETTING: 1250-bed urban academic medical center. PATIENTS: One hundred twenty-seven adults with neutropenic fever who received either imipenem-cilastatin or meropenem; imipenem-cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem. MEASUREMENTS AND MAIN RESULTS: Of the 127 patients, 40 received imipenem-cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem-cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in-hospital mortality (5% vs 7% vs 7%), and 30-day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively. CONCLUSION: The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem-cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.

Improving adherence to dyslipidemia medication guidelines in hospitalized diabetic patients using a technology-assisted pharmacist intervention.

We tested whether a technology-assisted pharmacist intervention improved physician adherence to guidelines for lipid-lowering therapy in diabetic patients. Computerized alerts identified diabetic patients above LDL-Cholesterol (LDL-C) goal. During Period 1 prescribing behavior was observed in both control and intervention physician groups without intervening. In Period 2, pharmacists conducted academic detailing with intervention group physicians. Control group physicians were observed. The intervention significantly improved the proportion of diabetic patients discharged on statin therapy.

Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections.

The objective of this study was to evaluate the relationship of the predicted pharmacodynamic parameters 24-h area under the inhibitory curve (AUIC=area under the concentration-time curve for 24h of dosing/minimum inhibitory concentration (AUC0-24/MIC) and time above the minimum inhibitory concentration (T>MIC) with clinical and microbiological outcomes in patients with bacteraemia and sepsis treated with cefepime or ceftazidime. Pharmacokinetic and pharmacodynamic parameters were derived for 76 of 107 patients enrolled in two prospective, randomised, clinical trials comparing cefepime with ceftazidime for the treatment of sepsis with bacteraemia, lower respiratory tract infection or complicated urinary tract infection. The relationships between the pharmacodynamic parameters and outcomes were examined. Whilst no significant differences in clinical outcomes were observed between cefepime and ceftazidime, there were significant differences in the pharmacodynamic analysis. Patients with an AUIC> or =250 had significantly greater clinical cure (79% vs. 33%; P=0.002) and bacteriological eradication (96% vs. 44%; P<0.001) than patients with an AUIC<250. Patients with T>MIC of 100% had significantly greater clinical cure (82% vs. 33%; P=0.002) and bacteriological eradication (97% vs. 44%; P<0.001) than patients with T>MIC of <100%. Both microbiological and clinical cure rates were suboptimal in patients receiving cefepime or ceftazidime for the treatment of serious infections if the AUIC was <250 or T>MIC was <100%.

Early clinical experience with anidulafungin at a large tertiary care medical center.

STUDY OBJECTIVE: To evaluate early clinical experience with anidulafungin. DESIGN: Retrospective cohort study. SETTING: Large, university-affiliated, tertiary care medical center. PATIENTS: All patients receiving anidulafungin between July 15, 2006, and January 15, 2007. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients received at least one dose of anidulafungin. Safety and tolerability were evaluated in all patients; efficacy outcomes were assessed in 13 patients who had a documented fungal infection and received anidulafungin for a minimum of 5 days. Common conditions at baseline were hepatic dysfunction (25 patients [71%]), severe sepsis (17 patients [49%]), and solid organ or hematopoietic stem cell transplantation (10 patients [29%]). Eight patients (23%) were receiving drugs with the potential to interact with echinocandins other than anidulafungin. Seventeen (49%) of the 35 patients received anidulafungin as empiric antifungal therapy. Anidulafungin was used to treat invasive candidiasis in seven patients (20%) and candidemia in 10 patients (29%); Candida albicans or Candida glabrata was isolated most frequently in these two infections combined (7 isolates each [41%]/17 infections). A favorable efficacy outcome was noted in 10 (77%) of 13 evaluable patients. One patient developed breakthrough Candida parapsilosis fungemia while receiving anidulafungin. Overall, anidulafungin was well tolerated, with only one patient having an infusion- related reaction. Anidulafungin was also well tolerated among patients receiving concomitant metronidazole. CONCLUSION: Anidulafungin was well tolerated and produced favorable outcomes in the majority of the patients evaluated. The availability of anidulafungin makes it a feasible option for antifungal therapy, particularly in patients who have hepatic dysfunction and in those who are receiving drugs than can interact with other echinocandins.

Daptomycin versus vancomycin for complicated skin and skin structure infections: clinical and economic outcomes.

STUDY OBJECTIVE: To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections. DESIGN: Prospective, open-label study. SETTING: Level 1 trauma center in Detroit, Michigan. PATIENTS: Fifty-three adult patients with complicated skin and skin structure infections at risk for methicillin-resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin. INTERVENTION: Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5-20 microg/ml. MEASUREMENTS AND MAIN RESULTS: Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001). CONCLUSIONS: Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost-effective alternative to vancomycin for complicated skin and skin structure infections.

Clinical outcomes and cost minimization with an alternative dosing regimen for meropenem in a community hospital.

STUDY OBJECTIVE: To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. DESIGN: Retrospective cohort study with a cost-minimization analysis. SETTING: A 417-bed, privately owned community hospital. PATIENTS: One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). CONCLUSION: An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

Impact of empirical-therapy selection on outcomes of intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus.

This study compares beta-lactam and vancomycin among intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus. Patients who received vancomycin had higher infection-related mortality, even if they were switched to beta-lactam once culture results became available; this relationship persisted after logistic regression analysis controlling for clinical characteristics.

Burden of methicillin-resistant Staphylococcus aureus: focus on clinical and economic outcomes.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major public concern. Hospital-acquired MRSA rates have steadily increased over the past 25 years, and the bacterial strain is making inroads to the community. The morbidity and mortality burden of MRSA infection is compounded by delayed or inappropriate antibiotic treatment, taking a toll on health care resources that are already stretched thin. Vancomycin has historically been the drug of choice for this pathogen because its broad spectrum can address the multidrug resistance of most MRSA infections. Despite its sustained in vitro microbiologic inhibitory activity, researchers are beginning to question the continued utility of vancomycin for MRSA infections. Evidence against vancomycin is most notable with regard to nosocomial pneumonia and skin and soft tissue infections. In addition, because vancomycin must be administered intravenously, patients typically require prolonged hospitalization, which further increases the cost of MRSA treatment and exposes patients to additional nosocomial infections. Recent studies have shown that antibiotics with good bioavailability, such as linezolid, can be given orally to facilitate early hospital discharge, thus alleviating the economic burden of MRSA infections. Several agents have been developed over the past decade that have excellent in vitro activity against MRSA. Further studies are needed to determine if these drugs can better eradicate MRSA than vancomycin and remedy the adverse outcomes frequently observed with this organism.

Epidemiology, risk factors, and outcomes of Candida albicans versus non-albicans candidemia in nonneutropenic patients.

BACKGROUND: Candidemia is a major cause of morbidity and mortality in hospitalized patients. OBJECTIVES: To describe the epidemiology of and risk factors for non-albicans candidemia (NAC) in nonneutropenic adults and the impact of NAC on patient outcomes and treatment cost. METHODS: We conducted a retrospective cohort analysis comparing demographics and risk factors for Candida albicans candidemia (CAC) versus NAC in 144 nonneutropenic patients with candidemia over a 6 year period (1997-2002) at Detroit Receiving Hospital. RESULTS: Candida species distribution included albicans (50%), parapsilosis (13%), tropicalis (10%), and glabrata (13%). Predominant species varied by patient care unit, with C. glabrata more common in the medical intensive care unit (ICU) and C. parapsilosis in the burn ICU. In multivariate analysis, NAC was associated with the absence of antibiotic use at the onset of candidemia, recent history of solid tumor, and male sex. NAC was not associated with an increase in mortality or length of stay compared with CAC, but was found to have a higher cost of antifungal therapy ($2030 vs $780; p = 0.05). CONCLUSIONS: The epidemiology of candidemia is complex and varies among the different patient care units. Specifically, patients appear less likely to develop NAC if they are receiving antibiotics at the onset of candidemia. Increased awareness of risk factors for NAC can be used to guide adequate initial antifungal therapy.

The economic effect of oral linezolid versus intravenous vancomycin in the outpatient setting: the payer perspective.

Oral antibiotic therapy can reduce complications and costs compared with intravenous (IV) therapy. The object of this study was to determine the health economic and resource utilization effects of outpatient treatment with oral linezolid relative to IV vancomycin. Longitudinal claims data from 80 health care plans were used. Patients 18 years and older, who did not have osteomyelitis, with a pharmacy claim for linezolid or vancomycin between January 1, 2002 and March 31, 2004 were eligible. Clinical and resource utilization data were collected for 12 months before and 35 days after treatment. Patients treated with linezolid were matched with controls treated with vancomycin, based on propensity scoring. Direct medical costs paid by health plans were compared. A total of 1,048 matched pairs were identified. Demographic and clinical characteristics were comparable between groups. Patients with linezolid claims had lower resource utilization versus those with vancomycin claims during follow-up, including fewer mean physician office visits (4.1+/-5.7 vs. 8.4+/-13.8 visits; P< .001); lab/diagnostic claims (6.3+/-18.0 vs. 10.4 +/-15.2 claims; P< .001); pharmacy claims (7.3+/-8.1 vs. 13.6+/-17.4 claims; P< .001); emergency room visits (9.7% vs. 13.9%; P= .003) and hospitalization (15.3% vs. 19.1%; P= .024). Patients receiving vancomycin were more likely to be hospitalized or have an emergency room visit than patients receiving linezolid. Mean total adjusted cost was 4,707 dollars less for linezolid compared with vancomycin (8,401dollars vs. 13,108 dollars; P< .001). Similar trends were observed for patients matched based on complicated skin and soft tissue infection diagnosis. Outpatient treatment with oral linezolid was associated with significantly lower resource utilization and total medical costs compared with IV vancomycin.

Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices.

OBJECTIVE: The goal of this investigation was to determine whether vancomycin pharmacokinetic indexes (eg, serum trough concentrations or area under the concentration curve [AUC] values) were associated with mortality for patients with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization who were identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p = 0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p = 0.941) did not differ between survivors and nonsurvivors. The stratification of the vancomycin trough concentrations and AUC values yielded no relationship with hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin trough concentrations or AUC values correlated with hospital outcome. Based on these results, aggressive dosing strategies for vancomycin (eg, trough concentrations of > 15 microg/mL) may not offer any advantage over traditional dose targets (range, 5 to 15 microg/mL).

Characteristics of patients with healthcare-associated infection due to SCCmec type IV methicillin-resistant Staphylococcus aureus.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) with the staphylococcal cassette chromosome mec (SCCmec) type IV allele is most commonly associated with community-acquired MRSA (CA-MRSA) infection; however, such organisms have also been identified in the healthcare setting. The objective of the present study was to characterize the epidemiology of and clinical outcomes associated with SCCmec-IV MRSA infection acquired in the healthcare setting, compared with infection caused by MRSA of other SCCmec types. DESIGN: We evaluated a cohort of 100 inpatients with MRSA infection that met the Centers for Disease Control and Prevention definition for healthcare-associated infection and compared the patients' demographic characteristics, the antimicrobial susceptibilities of the MRSA isolates, the infection types, and the associated clinical and microbiological outcomes. For each MRSA isolate, the SCCmec type and the presence of Panton-Valentine leukocidin (PVL) were determined by polymerase chain reaction methods. RESULTS: SCCmec-IV MRSA isolates were isolated from 53 patients (42% of these isolates were positive for PVL), and SCCmec-II or SCCmec-III MRSA was isolated from 47 patients (3% of these isolates were positive for PVL). No differences were noted between the patients in the SCCmec-II/III group and the patients in the SCCmec-IV group with respect to age (median, 55 vs 50 years); sex (77% vs 64% of patients were male); medical service (surgical service, 60% in both groups; ICU admission, 55% vs 53%), Acute Physiology and Chronic Health Evaluation II score (median, 8 vs. 7); infection type; or underlying comorbidities, except for presence of a burn wound (13% vs 2%; P < .04). Patients in the SCCmec-II/III group were more likely to have multiple sites of infection (P = .006) and a longer length of stay (LOS) prior to detection of MRSA than were patients in the SCCmec-IV group (median, 4 vs 1 days; P < .001). Total LOS was significantly greater for patients in the SCCmec-II/III, compared with those in the SCCmec-IV group (P = .006). Multiple logistic regression identified liver disease and longer LOS prior to detection of MRSA as predictors of infection with SCCmec-II/III MRSA. Rates of susceptibility to clindamycin, gentamicin, ciprofloxacin, levofloxacin, and tetracycline was significantly greater among SCCmec-IV MRSA isolates, compared with type II/III isolates (P < or = .05). Compared with SCCmec-IV isolates acquired in the community, the susceptibility rates among healthcare-associated SCCmec-IV isolates was significantly less for clindamycin, gentamicin, and levofloxacin, indicating that these organisms may quickly acquire resistance to non- beta -lactam antibiotics, as do SCCmec-II/III strains. CONCLUSIONS: SCCmec-IV MRSA appears to have become established in hospitals. The onset of infection caused by SCCmec-IV strains is earlier than the onset of infection with SCCmec-II/III strains; however, associated types of infection are similar. Infection with SCCmec-II/III MRSA is currently associated with an adverse impact on outcome, compared with infection with SCCmec-IV MRSA. Further research is warranted to determine the impact of SCCmec type IV strains in hospital settings.

Impact of linezolid on economic outcomes and determinants of cost in a clinical trial evaluating patients with MRSA complicated skin and soft-tissue infections.

BACKGROUND: In clinical trials, linezolid has demonstrated higher clinical cure rates and shorter hospital duration for patients than has vancomycin for the treatment of complicated skin and soft-tissue infections (cSSTIs). OBJECTIVE: To assess economic outcomes of linezolid versus vancomycin and evaluate determinants of treatment costs for cSSTIs. METHODS: Economic data were obtained from US subjects enrolled in a multinational, open-label, clinical trial of cSSTIs caused by suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects were randomized to receive intravenous or oral linezolid or intravenous vancomycin for 7-21 days. Costs for each patient were evaluated by applying nationally representative per diem hospital costs by hospital ward. Intravenous administration costs were applied to the duration of intravenous treatment. Factors contributing to the cost of therapy were evaluated using multivariate regression analysis. RESULTS: Seven hundred seventeen US patients were included in the study. Demographics were similar between treatment groups. Length of stay and duration of intravenous therapy were shorter for linezolid-treated patients. Mean +/- SD cost for intent-to-treat population patients treated with linezolid versus vancomycin was 4865 US dollars +/- 4367 versus 5738 US dollars +/- 5190, respectively (p = 0.017), and in the MRSA population was 4881 US dollars +/- 3987 versus 6006 US dollars +/- 5039, respectively (p = 0.041). Factors significantly associated with increased cost included vancomycin therapy, age, and comorbidities, including diabetes. After adjusting for all other factors, treatment with linezolid was associated with significantly lower treatment costs compared with vancomycin. CONCLUSIONS: Linezolid therapy was associated with improved clinical outcomes and significantly lower treatment costs than was vancomycin. The largest cost advantage was demonstrated in patients with documented MRSA cSSTIs.

Pharmacodynamic profiling of cefepime in plasma and cerebrospinal fluid of hospitalized patients with external ventriculostomies.

Population pharmacokinetic (PK) modeling and Monte Carlo simulation (MCS) were used to describe the pharmacodynamic profile of cefepime in the both plasma and cerebrospinal fluid (CSF). Plasma and CSF cefepime data were obtained from a PK study of 7 hospitalized patients with external ventricular drains. Concentration-time profiles in plasma and CSF were modeled using a 3-compartment model with zero-order infusion and first-order elimination and transfer. Estimates of the PK parameters were identified in the Big Non Parametric Adaptive Grid with adaptive gamma (BigNPAG) program of Leary, Jelliffe, Schumitzky, and Van Guilder. MCS (10,000 subjects) was performed to estimate the probability of attaining the targets of free plasma concentration (20% protein binding) and total drug CSF concentration of 50-100% T>minimal inhibitory concentration (MIC) for MICs 0.06-8 mg/L for cefepime 2 g, iv, every 8 h (0.5-h infusion); cefepime 2 g, iv, every 12 h (0.5-h infusion); and cefepime 2 g (0.5-h infusion) once and 250 mg/h continuous infusion. After the Bayesian step, the observed-predicted regression and r(2) for plasma and CNS were as follows: plasma, observed=0.984 x predicted+2.570, r(2)=0.944; CSF, observed=0.785 x predicted+0.868, r(2)=0.821. The median penetration of cefepime as measured by AUC(CSF)/AUC(plasma) was 7.8%. In the MCS, the target attainment rates in plasma for 60-70% fT>MIC were high at each MIC value between 0.03 and 8 microg/mL for each regimen examined. In CSF, none of the regimens achieved 50-100% T>MIC for>80% of patients for MICs>0.5 mg/L.

Prospective validation of an algorithm to identify hospitalized diabetic patients using administrative data.

To facilitate healthcare quality improvement initiatives, we previously developed an algorithm to identify diabetes mellitus (DM) patients using only electronically available administrative data. In this study, we have validated our prediction model, screening over 28,000 admissions and determining factors associated with false positive assignment. These factors will be incorporated into a revised algorithm.