Consequences of avoiding ß-lactams in patients with ß-lactam allergies.

BACKGROUND: The choice of empiric antibiotics for the treatment of gram-negative bacilli (GNB) bloodstream infections (BSIs) in patients presenting with a ß-lactam (BL) allergy is often a difficult decision given that these agents are first-line treatment in many guidelines. OBJECTIVE: We sought to compare rates of clinical failure between patients with a history of BL allergy who received either a BL or a non-ß-lactam (NBL). METHODS: Adult patients with a past medical history of BL allergy and receipt of antibiotics for treatment of a GNB BSI were included from 3 academic medical centers. Treatment groups were classified as BL or NBL groups based on the empiric antibiotics received. Clinical failure was assessed 72 to 96 hours after initiation of empiric antibiotics. Hypersensitivity reactions during receipt of antibiotic therapy for the index BSI were recorded. RESULTS: A total of 552 patients were included for analysis: 433 patients in the BL group and 119 patients in the NBL group. Clinical failure was higher in the NBL group compared with the BL group (38.7% vs 27.4%, P = .030). The most common cause of clinical failure was a temperature of greater than 38.0°C 72 to 96 hours after receipt of empiric antibiotics (NBL group: 22.7% vs BL group: 13.9%, P = .016). Hypersensitivity occurred in 16 (2.9%) of 552 patients. Thirteen (2.5%) of 552 patients experiencing hypersensitivity reactions were exposed to a BL during treatment for GNB BSI. CONCLUSION: Among patients with a BL allergy, use of BL antibiotics is associated with a lower rate of clinical failure. The low rate of hypersensitivity provides further evidence about the risk of cross-reactivity between BL classes. These results support the practice of using a BL from an alternative class for patients in need of gram-negative antibiotic coverage.

An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance.

INTRODUCTION: Pseudomonas aeruginosa nosocomial pneumonia (Pa-NP) is associated with considerable morbidity, prolonged hospitalization, increased costs, and mortality. METHODS: We conducted a retrospective cohort study of adult patients with Pa-NP to determine 1) risk factors for multidrug-resistant (MDR) strains and 2) whether MDR increases the risk for hospital death. Twelve hospitals in 5 countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and Spain, n = 3) participated. We compared characteristics of patients who had MDR strains to those who did not and derived regression models to identify predictors of MDR and hospital mortality. RESULTS: Of 740 patients with Pa-NP, 226 patients (30.5%) were infected with MDR strains. In multivariable analyses, independent predictors of multidrug-resistance included decreasing age (adjusted odds ratio [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90, 95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug-resistance, heart failure, increasing age, mechanical ventilation, and bacteremia were independently associated with in-hospital mortality in the Cox Proportional Hazards Model analysis. CONCLUSIONS: Among patients with Pa-NP the presence of infection with a MDR strain is associated with increased in-hospital mortality. Identification of patients at risk of MDR Pa-NP could facilitate appropriate empiric antibiotic decisions that in turn could lead to improved hospital survival.

Predictors of mortality among bacteremic patients with septic shock receiving appropriate antimicrobial therapy.

BACKGROUND: Factors capable of impacting hospital mortality in patients with septic shock remain uncertain. Our objective was to identify predictors of hospital mortality among patients who received appropriate antimicrobial therapy for bacteremic septic shock after accounting for severity of illness, resuscitation status, and processes of care. METHODS: We conducted a secondary subgroup analysis of a prospective severe sepsis cohort study. Patients with septic shock and positive blood cultures who received appropriate antimicrobial therapy were included. Univariable analyses were used to identify differences between hospital survivors and non-survivors, and a multivariable logistic regression model revealed independent determinants of hospital mortality. RESULTS: From January 2008 to December 2010, 58 of 224 included patients died in the hospital. Multivariable logistic regression analysis demonstrated 2 independent predictors of hospital mortality. These included continuous renal replacement therapy utilization within 48 hours of septic shock recognition (adjusted odds ratio [OR], 5.52; 95% confidence interval [CI], 1.94-16.34) and intra-abdominal infection (adjusted OR, 3.92; 95% CI, 1.47-10.79). Escherichia coli was independently associated with a lower risk of hospital mortality (adjusted OR, 0.34; 95% CI, 0.11-0.90). CONCLUSION: Intra-abdominal infection and continuous renal replacement therapy were associated with increased hospital mortality in patients with septic shock who received appropriate antimicrobial therapy. Our findings may be explained by suboptimal intra-abdominal infection management or inadequate antimicrobial concentration in these patients.

Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study.

BACKGROUND: The incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia. METHODS: A retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher's exact test while the student's t-test or Mann-Whitney U test were used for continuous variables. RESULTS: Ninety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033). CONCLUSIONS: Addition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.

Effect of continuous venovenous hemofiltration dose on achievement of adequate vancomycin trough concentrations.

The vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (≤30 ml/kg/h; n = 10) or high (>30 ml/kg/h; n = 77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough achievement occurred in only 32 (37%) patients. The primary endpoint of trough attainment significantly differed between HFR subgroups: 90% versus 30% in low- and high-HFR individuals, respectively (P < 0.001). Patients with subtherapeutic trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in those who achieved the trough goal. Irrespective of goal trough, an inverse correlation existed between HFR and serum vancomycin concentration (r = -0.423; P < 0.001). In the subgroup of 14 methicillin-resistant Staphylococcus aureus (MRSA) patients, trough achievement was similar to the aggregate cohort (36%). Mortality at 28 days was unrelated to trough achievement in both the overall sample (P = 0.516) and in culture-positive MRSA patients (P = 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.

Septic shock: a multidisciplinary response team and weekly feedback to clinicians improve the process of care and mortality.

OBJECTIVE: To evaluate the impact of weekly feedback to clinicians and the activation of a sepsis response team on the process of care and hospital mortality in patients with severe sepsis or septic shock. DESIGN: Prospective, interventional cohort study. SETTING: The medical intensive care unit of a tertiary, academic medical center. STUDY SUBJECTS: Patients with severe sepsis or septic shock consecutively treated in a medical intensive care unit. INTERVENTIONS: Daily auditing and weekly feedback, and sepsis response team activation. MEASUREMENTS AND MAIN RESULTS: During a 33-month study period, from January 2007 through September 2009, we performed daily screening of patients for severe sepsis or septic shock. Study periods were divided into baseline (screening only), daily auditing with weekly feedback, and sepsis response team activation. Comparisons among the three periods were made by using univariate and multiple logistic regression analyses. Compliance with the overall sepsis resuscitation bundle and its individual elements and hospital mortality were used as outcome measures. A total of 984 episodes of severe sepsis and septic shock were identified during the study periods, severe sepsis in 52 (5.3%) and septic shock in 932 (94.7%). The compliance rate with all elements of the sepsis resuscitation bundle increased from 12.7% at baseline to 37.7% and 53.7% during the weekly feedback and sepsis response team activation periods, respectively (p < .001). Overall hospital mortality rate was 30.3%, 28.3%, and 22.0% during baseline, weekly feedback, and sepsis response team periods, respectively (p = .029). Multiple logistic regression analysis showed that the sepsis response team was associated with reduced risk of hospital death (odds ratio, 0.657; 95% confidence interval, 0.456-0.945; p = .023) whereas hepatic cirrhosis, hepatic failure, leukemia, multiple myeloma, transfer from the same hospital ward, do-not-resuscitate status at the recognition of severe sepsis/septic shock, and lactate level were associated with increased risk of death. CONCLUSIONS: In septic shock, the activation of the sepsis response team in combination with weekly feedback increases the compliance with the process of care and reduces hospital mortality rate.

Novel Use of Text-Bot Automation for Residency Recruitment.

Purpose. To describe the employment of an automated text messaging text-bot during the 2019 American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting Residency Showcase and its impact on the number of applications received for the postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) pharmacy residency programs at a medium-sized community hospital. Methods. Visitors at the residency showcase booth were asked to text a code word to a program number. The text-bot collected the visitor's contact information and program of interest (PGY1 or PGY2). A series of automated messages were sent to all visitors following the showcase and up until the residency application deadline. Results. 71% (20/28) of visitors to the program's showcase booth registered with the text-bot and of these, 65% (13/20) submitted applications to the residency program in phase I of the match. Both the PGY1 and PGY2 programs saw an increase in the amount of applications received compared to previous year. Conclusion. A text messaging text-bot may be a useful residency recruitment tool.

Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria.

OBJECTIVE: To identify predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia (VAP) attributed to potentially antibiotic-resistant Gram-negative bacteria (PARGNB) [Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia]. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. PATIENTS: Adult patients requiring hospitalization with microbiologically confirmed VAP attributed to PARGNB. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Seventy-six patients with VAP attributed to PARGNB were identified over a 5-year period. Nineteen patients (25.0%) died during hospitalization. Patients receiving their first dose of appropriate antibiotic therapy within 24 h of BAL sampling had a statistically lower 30-day mortality rate compared to patients receiving the first dose of appropriate therapy >24 h after BAL (17.2% vs 50.0%; p = 0.005). VAP due to Acinetobacter species was most often initially treated with an inappropriate antibiotic regimen, followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Overall, total hospitalization costs were statistically similar in patients initially treated with an inappropriate antibiotic regimen compared to an appropriate regimen ($68,597 +/- $55,466 vs $86,644 +/- $64,433; p = 0.390). CONCLUSIONS: These data suggest that inappropriate initial antibiotic therapy of microbiologically confirmed VAP attributed to PARGNB is associated with greater 30-day mortality. High rates of VAP attributed to antibiotic-resistant bacteria (eg, Acinetobacter species) may require changes in the local empiric antibiotic treatment of VAP in order to optimize the prescription of appropriate initial therapy.

Role of corticosteroids in the management of acute respiratory distress syndrome.

BACKGROUND: Evidence exploring the use of corticosteroids for acute respiratory distress syndrome (ARDS) has targeted various stages of disease progression, from preventing ARDS in high-risk patients to halting disease evolution once ARDS has developed. OBJECTIVE: The aim of this review was to evaluate randomized, controlled trials describing the role of corticosteroids in preventing and treating ARDS. METHODS: English-language randomized, controlled trials were identified using MEDLINE via PubMed and EMBASE searches (key terms: acute respiratory distress syndrome, acute lung injury, and corticosteroids; years: 1968-January 2008). RESULTS: A total of 10 trials were found and included in this analysis. Trials describing the role of high-dose corticosteroids compared with controls in preventing ARDS found no benefit, with the range of occurrence of ARDS in at-risk populations from 14% to 64% and absolute increases in mortality from 4% to 31%. Conflicting evidence was found for treating late-phase ARDS with corticosteroids, with 13% hospital mortality among patients receiving corticosteroids versus 63% with controls (P = 0.03) in one small study, but no significant difference was found when evaluating 60-day mortality (corticosteroid group, 29.2% vs control, 28.6%) in another investigation. The use of high-dose corticosteroids for the treatment of early phase ARDS was not associated with significant differences in 45-day mortality (methylprednisolone, 60% vs control, 63%). However, one trial found that methylprednisolone taper for early ARDS was associated with significant improvement in lung function or extubation (69.8% vs 35.7%; P = 0.002), fewer days on mechanical ventilation (median, 5.0 vs 9.5; P = 0.002), higher intensive care unit survival (79.4% vs 57.4%; P = 0.03), but similar rates of hospital survival (methylprednisolone, 76.2% vs control, 57.1%; P = NS). CONCLUSIONS: Data from clinical trials did not support the use of short-course, high-dose corticosteroids for preventing ARDS or for the treatment of early ARDS. Longer-course corticosteroids have not conclusively been associated with improved survival in the treatment of late-phase ARDS but have provided some benefits in other markers of disease severity in this setting and in early phase ARDS. Published trials support the administration of low- to moderate-dose corticosteroids in the treatment of early (<7 days) and late-phase (days 7\2-14) ARDS, but this evidence is controversial.

Road Map for Research Training in the Residency Learning Experience.

The American Society of Health-System Pharmacists residency accreditation standards require all postgraduate residency training programs to teach and evaluate a resident's ability to advance practice through project development and presentation, underscoring the importance of conducting research in today's professional climate. Although many residents express strong interest in research participation and contributing to the medical literature, many obstacles to publication have been identified. We aim to illustrate a deliberate approach to teaching this material and structuring the longitudinal experience in a way that maximizes resources to overcome these barriers. Such efforts should aid residents, advisors, and program directors in establishing curriculum which leads to successful completion and publication of pharmacy resident's research projects.

Implementation of a pharmacogenomics education program for pharmacists.

PURPOSE: The development, implementation, and evaluation of a pharmacogenomics education program for pharmacists in a large, integrated multicampus health system are described. SUMMARY: Pharmacogenomics has been described as tailoring medications to each patient's unique genetic sequence with the goals of minimizing harmful effects and optimizing therapeutic effects. Pharmacists are uniquely trained to lead the implementation of pharmacogenomics in clinical care. After assessment of pharmacists' comfort with pharmacogenomics, different approaches were explored to develop, pilot test, and disseminate pharmacogenomics education across a multicampus academic medical center. Limited success with large-audience, single-lecture didactic education led to development and delivery of targeted, competency-based online modules using the institution's academic virtual learning environment and course management system. Implementation steps included (1) collaboration with the Mayo Clinic Center for Individualized Medicine to create an interprofessional development team and project charter, (2) galvanizing pharmacy leadership support across multiple campuses, (3) development of competency-based interactive modules, and (4) assessment of the quality of and learner satisfaction with the modules. Significant improvements in competency scores were observed with each module and across the multiple campuses. Satisfaction with the education program was assessed at the end of a 4-module series. CONCLUSION: A pharmacogenomics educational program targeting pharmacists was developed through interprofessional collaboration and provided a novel opportunity to construct an educational infrastructure to support enterprise health-system campuses with limited educational resources.

Increasing incidence of sterile-site infections due to non-multidrug-resistant, oxacillin-resistant Staphylococcus aureus among hospitalized patients.

The incidence of community-associated, healthcare-associated, and hospital-acquired sterile-site infections due to methicillin-resistant Staphylococcus aureus (MRSA) isolates and the susceptibility of the isolates to non- beta -lactam antibiotics were evaluated for 549 hospitalized patients during a 3-year period. The incidence of community-associated MRSA infection increased significantly. The annual percentage of MRSA isolates from cases of healthcare-associated and hospital-acquired infection that were susceptible to 3 or more non- beta -lactam antibiotics increased significantly.

Implementation of an interprofessional clinical pharmacology selective learning experience for pharmacy residents and medical students.

PURPOSE: The implementation of an interprofessional clinical pharmacology selective (CPS) learning experience for pharmacy residents and medical students is described. SUMMARY: The opportunity for pharmacy residents to provide didactic lectures at a college of pharmacy and to develop teaching and preceptor skills with experiential pharmacy students may be limited by institution-specific affiliations and geographic location. In order to overcome these barriers, the Mayo Clinic Hospital postgraduate year 1 (PGY1) pharmacy residency program implemented an interprofessional learning experience in which pharmacy residents serve the role of preceptors for first- and second-year medical students on a CPS. Medical students at the Mayo Medical School (MMS) work alongside the PGY1 resident to develop patient-specific, medication problem lists and gain an appreciation for pharmacy-focused interventions. Medical students teach pharmacy residents diagnostic, pathophysiologic, and patient-assessment considerations related to the medical school's curriculum. The clinical rounds component of the CPS allows for resident achievement of ASHP competency area R4, which focuses on the design of an effective educational activity; selection of a preceptor role; employment of instruction, modeling, coaching, and facilitation; use of effective presentation skills; generation of objective-based learner assessment questions; and identification of areas for continuous improvement. CONCLUSION: The Mayo Clinic Hospital PGY1 pharmacy residency program and MMS successfully implemented an innovative learning experience to promote interprofessional education between pharmacy residents and medical students. The program establishes collaborative relationships early in students' professional careers and allows for attainment of the ASHP-required competency area R4 through delivery of a CPS to medical students.

Assessment of a modified 4T scoring system for heparin-induced thrombocytopenia in critically ill patients.

PURPOSE: The purpose of the study is to determine if a modified 4T (m4T) scoring system, which omits clinical evaluation of other thrombocytopenic etiologies, is different from the 4T scoring system's probability to predict a positive heparin-induced thrombocytopenia (HIT) laboratory test in the intensive care unit. MATERIALS AND METHODS: This is a single-centered retrospective analysis of critically ill adults who had an enzyme-linked immunosorbent assay antiplatelet factor 4 antibody (ELISA anti-PF4 Ab) ordered. Patients were identified as HIT positive (optical density, ≥0.40) or HIT negative (optical density, <0.40) based on the ELISA anti-PF4 Ab. Both 4T and m4T scores were calculated, and the diagnostic accuracy was compared using paired receiver operating characteristic curves. RESULTS: A total of 1487 adult intensive care unit patients with an ELISA anti-PF4 Ab ordered between January 2007 and December 2009 were eligible for study enrollment. Application of exclusion criteria and random selection yielded a total of 232 patients included for analysis (58 HIT-positive and 174 HIT-negative patients). The area under the curve for the 4T and m4T scores were 0.683 (95% confidence interval, 0.604-0.762) and 0.680 (95% confidence interval, 0.600-0.759), respectively (P=.065). CONCLUSION: This study does not show a difference in the probability of the m4T and 4T scoring systems to predict a positive ELISA anti-PF4 Ab test in the critically ill patient population. Further prospective studies are needed to validate the m4T scoring system.

Derivation of urine output thresholds that identify a very high risk of AKI in patients with septic shock.

BACKGROUND AND OBJECTIVES: To promote early detection of AKI, recently proposed pretest probability models combine sub-Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria with baseline AKI risk. The primary objective of this study was to determine sub-KDIGO thresholds that identify patients with septic shock at highest risk for AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective analysis of 390 adult patients admitted to the medical intensive care unit (ICU) of a tertiary, academic medical center with septic shock between January 2008 and December 2010. Hourly urine output was collected from the time of septic shock recognition (hour 0) to hour 96, urine catheter removal, or ICU discharge (whichever occurred first). All available serum creatinine (SCr) measurements were collected until hour 96. The AKI pretest probability model was assessed during the first 12 hours of resuscitation and included the initial episode of oliguria, increase from baseline to peak SCr level, and Acute Physiology and Chronic Health Evaluation (APACHE) III score in a multivariable receiver-operator characteristic (ROC) analysis. The primary outcome was the incidence of stage II or III (stage II+) AKI defined by KDIGO criteria. Secondary outcomes included the need for RRT and 28-day mortality. RESULTS: Ninety-eight (25%) patients developed stage II+ AKI after septic shock recognition. APACHE III score and increase in SCr level in the first 12 hours were not statistically associated with stage II+ AKI in multivariable ROC analysis. Consecutive oliguria for 3 hours had fair predictive ability for achieving stage II+ AKI criteria (area under ROC curve, 0.73; 95% confidence interval [95% CI], 0.68 to 0.78), and oliguria for 5 hours demonstrated optimal accuracy (82%; 95% CI, 79% to 86%). CONCLUSIONS: Three to 5 hours of consecutive oliguria in patients with septic shock may provide a valuable measure of AKI risk. Further validation to support this finding is needed.

The importance of fluid management in acute lung injury secondary to septic shock.

BACKGROUND: Recent studies have suggested that early goal-directed resuscitation of patients with septic shock and conservative fluid management of patients with acute lung injury (ALI) can improve outcomes. Because these may be seen as potentially conflicting practices, we set out to determine the influence of fluid management on the outcomes of patients with septic shock complicated by ALI. METHODS: A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, MO) and in the medical ICU of Mayo Medical Center (Rochester, MN). Patients hospitalized with septic shock were enrolled into the study if they met the American-European Consensus definition of ALI within 72 h of septic shock onset. Adequate initial fluid resuscitation (AIFR) was defined as the administration of an initial fluid bolus of >or= 20 mL/kg prior to and achievement of a central venous pressure of >or= 8 mm Hg within 6 h after the onset of therapy with vasopressors. Conservative late fluid management (CLFM) was defined as even-to-negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset. RESULTS: The study cohort was made up of 212 patients with ALI complicating septic shock. Hospital mortality was statistically lowest for those achieving both AIFR and CLFM and higher for those achieving only CLFM, those achieving only AIFR, and those achieving neither (17 of 93 patients [18.3%] vs 13 of 31 patients [41.9%] vs 30 of 53 patients [56.6%] vs 27 of 35 [77.1%], respectively; p < 0.001). CONCLUSIONS: Both early and late fluid management of septic shock complicated by ALI can influence patient outcomes.

Methicillin-resistant Staphylococcus aureus sterile-site infection: The importance of appropriate initial antimicrobial treatment.

OBJECTIVE: The first goal of this investigation was to determine the rate of appropriate initial antimicrobial administration to patients with methicillin-resistant Staphylococcus aureus (MRSA) sterile-site infections. Our second goal was to evaluate the influence of appropriate initial treatment of MRSA sterile-site infection on outcome. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization identified to have an MRSA sterile-site infection. INTERVENTIONS: Retrospective data collection from automated hospital and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Five hundred forty-nine patients with S. aureus sterile site infections were identified during a 3-yr period (January 2002 through December 2004). One hundred twenty-seven (23.1%) died during hospitalization. Hospital mortality was statistically greater for patients receiving inappropriate initial antimicrobial treatment (n = 380) within 24 hrs of a positive culture than for those receiving appropriate initial treatment (n = 169) (26.1% vs. 16.6%; p = .015). Multiple logistic regression analysis identified inappropriate initial antimicrobial treatment (adjusted odds ratio [AOR], 1.92; 95% confidence interval [CI], 1.48-2.50; p = .0134), vasopressor administration (AOR, 5.49; 95% CI, 4.08-7.38; p < .001), and increasing age (1-yr increments) (AOR, 1.03; 95% CI, 1.02-1.04; p < .001) as independent determinants of hospital mortality. CONCLUSIONS: Inappropriate initial antimicrobial treatment of MRSA sterile-site infections is common and is associated with an increased risk of hospital mortality. Appropriate antimicrobial treatment of MRSA sterile-site infections may be maximized by increased use of initial empirical antimicrobial treatment regimens targeting MRSA in patients at risk for this infection until organism identification and susceptibility become known.