Three ways to advocate for the economic value of the pharmacist in health care.

Numerous studies have demonstrated positive therapeutic and economic outcomes associated with pharmacist-provided care. However, public policy on provider status with subsequent payment for non-dispensing services has been slow to reflect an expanded pharmacist role. It is important for the public to understand the value of a pharmacist outside of the drug distribution system. Pharmacists and other health care and public health practitioners must share this information to further knowledge and affect policies and systems that can most effectively include pharmacists fully in the health care system. The 3 main areas identified in which the pharmacist has economic impact are decreased total health expenditures, decreased unnecessary care, and decreased societal costs. Evidence supports the economic value of the pharmacist; however, public opinion and political movements supporting patients' access to pharmacist-provided care are variable. Strategies to advocate and effect change include advocating to elected leaders for policy change and advocating to other health professionals, patients, and community members to better their understanding of the positive economic value of pharmacist-provided care. Through prioritizing community outreach and legislator education, pharmacist advocates can leverage 3 key areas in which pharmacists have economic value to advance policy and increase patients' access to care.

Developing a Business Plan for Critical Care Pharmacy Services.

Critical care medicine has grown from a small group of physicians participating in patient care rounds in surgical and medical intensive care units (ICUs) to a highly technical, interdisciplinary team. Pharmacy's growth in the area of critical care is as exponential. Today's ICU requires a comprehensive pharmaceutical service that includes both operational and clinical services to meet patient medication needs. This article provides the elements for a business plan to justify critical care pharmacy services by describing the pertinent background and benefit of ICU pharmacy services, detailing a current assessment of ICU pharmacy services, listing the essential ICU pharmacy services, describing service metrics, and delineating an appropriate timeline for implementing an ICU pharmacy service. The structure and approach of this business plan can be applied to a variety of pharmacy services. By following the format and information listed in this article, the pharmacy director can move closer to developing patient-centered pharmacy services for ICU patients.

Pharmacokinetic study in pigs and in vitro metabolic characterization in pig- and human-liver microsomes reveal marked differences in disposition and metabolism of tiletamine and zolazepam (Telazol).

1. An equal-dose combination of tiletamine and zolazepam (Telazol®) is used as a veterinary anesthetic. There also have been reports of human abuse of Telazol®. The pharmacokinetics and metabolic fate of tiletamine and zolazepam and the rationale for their administration as an equal-dose combination are unclear. 2. The single-dose pharmacokinetics of intramuscular tiletamine and zolazepam (3 mg/kg each) in 16 Yorkshire-crossbred pigs were determined. The metabolites of tiletamine and zolazepam in pig plasma and urine were identified by mass spectrometry. The metabolic stability of tiletamine and zolazepam and the kinetics of formation of their metabolites by pig- and human-liver microsomes were determined. 3. Higher concentrations of zolazepam were observed in pig plasma and it was cleared more slowly compared to tiletamine (apparent clearance: 11 versus 134 l/h; half-life: 2.76 versus 1.97 h). Three metabolites of zolazepam and one metabolite of tiletamine were identified in pig urine, plasma and in microsomal incubations. In vitro formation of each of these metabolites in microsomes was biphasic involving a high-affinity/low-capacity and a low-affinity/high-capacity enzyme. The in vitro metabolic stability of tiletamine was considerably lower compared to zolazepam. 4. These results collectively point to major pharmacokinetic and metabolic differences between the two components of this fixed-dose anesthetic combination.

Current issues and recommendations to manage prescription drug benefits for public health programs.

Higher scrutiny is befalling public payors regarding drug costs and patient access to medications. These issues exist in a complex contractual environment where minimal oversight of pharmacy claim adjudication and reimbursement practices can occur. The complexity of prescription benefits, and the lack of defined expectations or accountability in the system contribute to a sense of frustration by the public. Key areas of improvement for this sector of the health care industry include legislative and regulatory shifts requiring ongoing analyses, reporting, and accountability of pharmacy benefit managers (PBMs) in order to improve payment transparency. These improvements will enable plans to eliminate misaligned incentives in the industry and drive value. Changes in public sector programs should be comprehensive in their approach so that the policy will result in a reduction in costs, enhanced patient access, better patient safety, and improved health outcomes.

Drug metabolism in hemorrhagic shock: pharmacokinetics of selective markers of cytochrome-P450 2C9, 2D6, and 3A4 enzyme activities in a porcine model.

BACKGROUND: Cytochrome-P450 enzymes metabolize most administered drugs. A variety of clinical conditions affect the CYP system. However, the effect of hemorrhagic shock on CYP-mediated drug metabolism in clinical setting or in clinically applicable in-vivo models is largely unknown. Simultaneous administration of multiple CYP enzyme-selective drugs is a technique to ascertain a population's metabolic profile with a limited number of subjects. MATERIALS AND METHODS: Pigs were used as experimental animals as they possess CYP functionality similar to humans. Three probe drugs (dextromethorphan [CYP2D6], flurbiprofen [CYP2C9], and midazolam [CYP3A4]; doses: 0.5, 0.25, and 0.5 mg/kg, respectively) were administered intravenously to six Yorkshire-crossbred pigs in healthy state. Hemorrhagic shock was induced in six (four from healthy group after a 7-d washout period and two additional) pigs and the same doses of probe drugs were administered after a 14-h resuscitation phase. Blood samples were collected periodically in both phases and analyzed for parent drugs and metabolites (dextrorphan, 4'-hydroxy-flurbiprofen and 1'-hydroxy-midazolam) to calculate pharmacokinetic parameters. A comprehensive set of biochemical and physiologic markers of shock was also recorded. RESULTS: No changes in parent drug clearances were observed post-shock. Extensive metabolite formation with apparent higher exposure to total (conjugated and unconjugated) dextrorphan (p = 0.08), 4'-hydroxy-flurbiprofen (p = 0.11) and 1'-hydroxy-midazolam (p = 0.09) were observed post-shock. CONCLUSIONS: The metabolic capacity of CYP enzymes did not appear to be severely hindered in resuscitative phase of hemorrhagic shock. Diminished renal secretory function caused by hemorrhagic shock may be the cause of metabolite accumulation in plasma.

Report of the 2018-2019 Strategic Engagement Standing Committee.

EXECUTIVE SUMMARY. Strategic engagement is critical to the success of colleges and schools of pharmacy in expanding pharmacy and public health practice, meeting programmatic needs, and fulfilling institutional missions. The AACP 2019-2020 Strategic Engagement Committee was charged with exploring faculty leadership and development as they relate to strategic engagement, considering challenges and barriers to faculty participation and identifying successes in faculty engagement and opportunities for professional development. The committee reviewed literature and examples regarding strategic engagement across academic pharmacy, with strategic engagement understood as being part of the service mission of academic institutions. The committee found faculty service is often not rewarded or recognized equally to efforts in research and education, including in promotion and tenure. The perceived low value often accorded to strategic engagement efforts, coupled with lack of time and low priority for the work, are barriers to faculty participation in strategic engagement. Service missions thrive when supported by institutional culture, faculty and alumni role models and administration priorities. The committee also found that there is no defined path to leadership in most national organizations, a limited number of leadership positions and a lack of awareness regarding these positions. However, strategic engagement with organizations can open doors and increase visibility for faculty, leading to enhanced opportunities and improved scholarship. Engagement efforts can be particularly successful when aligned with faculty interests and school and departmental priorities. Based on the committee's work, the following recommendations are provided to AACP for consideration.Recommendation #1 - AACP should create a pathway or exemplar stories of members who have become leaders within the Academy including institutional and volunteer leadership roles.Recommendation #2 - AACP should provide an organizational chart to outline the reporting structures, as well as the policy development process to help members understand how AACP works and points of entry for involvement.Recommendation #3 - AACP should develop an initiative to "groom" faculty for leadership roles including providing tools/training programs for emerging leaders within the Academy.Recommendation #4 - AACP should consider creating a community for targeted groups of faculty, eg, tenured/tenure-track and non-tenure track to address leadership development and engagement based on member interest.Recommendation #5 - AACP should establish a "service mentors" program to match current and past leaders with members interested in enhancing their involvement in the association.

Forging a critical alliance: Addressing the research needs of the United States critical illness and injury community.

OBJECTIVE: Discuss the research needs of the critical illness and injury communities in the United States. DATA SOURCES: Workshop session held during the 5 National Institutes of Health Symposium on the Functional Genomics of Critical Illness and Injury (November 15, 2007). STUDY SELECTION: The current clinical research infrastructure misses opportunities for synergy and does not address many important needs. In addition, it remains challenging to rapidly and properly implement system-wide changes based upon reproducible evidence from clinical research. DATA EXTRACTION: Author presentations, panel discussion, attendee feedback. DATA SYNTHESIS: The critical illness and injury research communities seek better communication and interaction, both of which will improve the breadth and quality of acute care research. Success in meeting these needs should come from cooperative and strategic actions that favor collaboration, standardization of protocols, and strong leadership. An alliance framed on common goals will foster collaboration among experts to better promote clinical trials within the critically ill or injured patient population. CONCLUSIONS: The U.S. Critical Illness and Injury Trials Group was funded to create a clinical research framework that can reduce the barriers to investigation using an investigator-initiated, evidence-driven, inclusive approach that has proven successful elsewhere. This alliance will provide an annual venue for systematic review and strategic planning that will include framing the research agenda, raising awareness for the value of acute care research, gathering and promoting best practices, and bolstering the critical care workforce.

Multicenter implementation of a consensus-developed, evidence-based, spontaneous breathing trial protocol.

OBJECTIVE: Evidence-based practice recommendations abound, but implementation is often unstructured and poorly audited. We assessed the ability of a peer network to implement an evidence-based best practice protocol and to measure patient outcomes. DESIGN: Consensus definition of spontaneous breathing trial followed by implementation in eight academic medical centers. SETTING: Six medical, two surgical, and two combined medical/surgical adult intensive care units among eight academic medical centers. STUDY POPULATION: Patients initiating mechanical ventilation through an endotracheal tube during a 12-wk interval formed the study population. INTERVENTIONS: Adoption and implementation of a common spontaneous breathing trial protocol across multiple intensive care units. MEASUREMENTS AND MAIN RESULTS: Seven hundred five patients had 3,486 safety screens for conducting a spontaneous breathing trial; 2072 (59%) patients failed the safety screen. Another 379 (11%) patients failed a 2-min tolerance screen and 1,122 (34%) patients had a full 30-120 min spontaneous breathing trial performed. Seventy percent of eligible patients were enrolled. Only 55% of passing spontaneous breathing trials resulted in liberation from mechanical ventilatory support before another spontaneous breathing trial was performed. CONCLUSIONS: Peer networks can be effective in promoting and implementing evidence-based best practices. Implementation of a best practice (spontaneous breathing trial) may be necessary for, but by itself insufficient to achieve, consistent and timely liberation from ventilator support.

The science of implementation: changing the practice of critical care.

PURPOSE OF REVIEW: Few would disagree that evidence from clinical research should be brought to the bedside in an efficient and equitable manner. Unfortunately, this common agreement does not result in practice change at the bedside where delayed and variable implementation is common. Recognition of this gap has resulted in a new discipline called implementation science that seeks to understand the reasons for slow adoption of clinical therapeutics and to discover effective strategies that accelerate practice change. This article reviews implementation theory and strategies and their effectiveness and relevance to critical care. RECENT FINDINGS: The absence of a proven effective framework for implementing clinical practice change has resulted in a patchwork of interventions in ambulatory and acute care medicine. There is an increasing appreciation that interventions should be undertaken only after careful, theory-based examination of the source and strength of the evidence, the organizational and professional context in which the change will be made, and the availability of facilitating methods. Barriers to implementing sepsis management programs have been identified and, in some cases, overcome. SUMMARY: Changing clinical practice is sometimes as difficult as the basic science and clinical trials work that led to the discovery of beneficial therapies. Investigators are now beginning to develop and test more theory-based implementation models that are relevant to the clinical environment. A proportion of the resources used in developing an ICU guideline or protocol must be dedicated to the implementation strategy for successful adoption. ICUs are ideal organizations to test new approaches in implementation science. Intensive care professionals should insist that their practice environment have both a culture that is supportive of adopting new practices and adequate resources to implement them into patient care.

Simultaneous analysis of cytochrome P450 probes-dextromethorphan, flurbiprofen and midazolam and their major metabolites by HPLC-mass-spectrometry/fluorescence after single-step extraction from plasma.

Cytochrome P450 enzymes catalyze oxidative metabolism of most pharmaceutical compounds. Consequently dextromethorphan, flurbiprofen, midazolam and other compounds are commonly used as probe substrates to evaluate cytochrome P450 function in humans. A "cocktail" approach employing simultaneous administration of two or more of the probe substrates has been used by various investigators in recent years. An analytical strategy to simultaneously extract and analyze dextromethorphan, flurbiprofen and midazolam and their major metabolites (dextrorphan, 4'-hydroxy-flurbiprofen and 1'-hydroxy-midazolam) by HPLC-MS/fluorescence was developed and is described here. The three probe substrates and their major metabolites were extracted simultaneously by means of a solid-phase (Bond Elut Certify cartridges) extraction procedure from 200 microl of pig plasma. The extraction efficiency was more than 79.5% for each of the six analytes. The extracted compounds were chromatographically separated on a Luna C8(II) column (50 mm Lx3 mm ID) in a single run of 20 min and analyzed by either fluorescence (flurbiprofen and 4'-hydroxy-flurbiprofen) or selective ion monitoring (dextromethorphan, dextrorphan, midazolam and 1'-hydroxy-midazolam) with positive electrospray ionization. The limit of quantification was 2.5 ng/ml for midazolam and 5 ng/ml for the other five analytes. The assay was precise and accurate (error: -9.1 to 12.1) with total CVs of 13.9% or better for each of the 6 analytes. This method was used to analyze concentrations of the three probes and their metabolites in plasma after intravenous administration to a healthy pig.

Determination of constituents of Telazol--tiletamine and zolazepam by a gas chromatography/mass spectrometry-based method.

Tiletamine and zolazepam injection (Telazol) is used in veterinary surgical practice to induce short-term anesthesia and also to immobilize wild animals. The present work describes a sensitive method to measure tiletamine and zolazepam concentrations in plasma by means of GC/EI-MS on a 5% phenyl/95% methylpolysiloxane column. A simple liquid extraction procedure with ethyl acetate was used to isolate the two compounds and the same were separated and analyzed by GC/MS without derivatization. A formal validation of the assay demonstrated good accuracy and precision for both tiletamine (98-100.8%; C.V.total < 6.7%) and zolazepam (98.3-103.4; C.V.total < 13.2%). With 500 microl of plasma, the limits of quantification for both tiletamine and zolazepam were found to be 10 ng/ml. Both compounds were stable after three freeze-thaw cycles. The assay was used to analyze plasma samples collected from a pig after intramuscular administration of 10 mg/kg of Telazol. The plasma concentration-time profile of tiletamine and zolazepam from this representative pig is also provided.

Drug-associated disease: cytochrome P450 interactions.

Critically ill patients generally are older, frequently have organ failure, and commonly receive multiple medications, all of which make them susceptible to adverse effects of drugs. Drug interactions are a common adverse effect, and many are predictable based on understanding the mechanisms that underlie drug interactions. This article identifies commonly used medications in critically ill patients and the associated drug interactions that may occur with emphasis on the cytochrome P450 enzyme system.

Current issues regarding the use of drotrecogin alfa (activated).

The key issues clinicians are facing regarding drotrecogin alfa (activated) include questions concerning the pathophysiology and appropriate patient selection for administration of this drug. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, the efficacy of drotrecogin alfa (activated) was demonstrated in patients with severe sepsis. Because of this trial's strict inclusion and exclusion criteria, however, the applicability of the study criteria to different types of patients raises important issues. Coupling the data from the PROWESS trial with additional information being gained from expanding clinical experience, as well as additional studies, clinicians will be able to better understand and refine the use of activated protein C within their respective practices.

Recombinant human activated protein C in severe sepsis.

The role of activated protein C (APC) in coagulation, inflammation, and fibrinolysis and the pharmacology, pharmacokinetics, and trials of recombinant human activated protein C (rhAPC), or drotrecogin alfa (activated), in sepsis are described. Protein C, a naturally occurring vitamin K-dependent serine protease in the blood, remains inactive until exposed to the thrombin-thrombomodulin complex. This change between the inactive and active forms occurs constantly in humans and serves to balance the coagulation cascade. APC functions in concert with protein S as an anticoagulant, a fibrinolytic agent, and an antiinflammatory agent. In response to serious infection, a procoagulant process is activated leading to thrombin and fibrin deposition in small vessels that results in decreased blood flow, decreased oxygen delivery, and organ failure. The body's natural defense during severe sepsis is to activate protein C through the thrombin-thrombomodulin complex in an attempt to restore the imbalance of the hemostatic systems. However, APC has a short half-life, and the pool of circulating protein C is rapidly depleted in severe sepsis. Low protein C levels have been correlated with poor outcome in patients with severe sepsis and in animal models. These observations led to a Phase III safety and efficacy trial of drotrecogin alfa (activated) that demonstrated a significant improvement in mortality compared with placebo (24.7% versus 30.8%). This 6.1% absolute difference in mortality translates to a 19.4% reduction in relative risk of death in the treated patients. The proper use of drotrecogin alfa (activated) will require careful consideration of appropriate patients to treat and further studies in patient populations that were excluded from the Phase III trial, as well as possible modification of dosing schemes on the basis of patient response.

Appraisal of four novel approaches to the prevention and treatment of sepsis.

PURPOSE: Four novel approaches to the management of sepsis are discussed. SUMMARY: Drotrecogin alfa (activated) has FDA-approved labeling for use in the treatment of severe sepsis. Risk of bleeding and identification of the most suitable patients have been the major issues related to use of this drug. Tight glycemic control and early goal-directed therapy (EGDT) are promising supportive strategies. Both have challenged existing views regarding safe glucose levels and the usefulness of increased oxygen delivery in sepsis. The routine maintenance of euglycemia is resource intensive, however, and benefits during treatment of sepsis are unclear. Very early initiation of measures to optimize hemodynamic variables and the ability to identify patients with cryptic shock appear to be key reasons for successful EGDT. The use of corticosteroids for septic shock has been extensively researched and has provoked controversy. Selection of patients likely to benefit on the basis of relative adrenal insufficiency and prolonged treatment may account for recently observed positive results. A model for combining the four strategies is proposed. CONCLUSION: Novel strategies for treating sepsis include drotrecogin alfa (activated), tight glycemic control, EGDT, and low-dose corticosteroids.

Physical and chemical compatibility of drotrecogin alfa (activated) with 34 drugs during simulated Y-site administration.

PURPOSE: The physical and chemical compatibility of drotrecogin alfa (activated) (recombinant human activated protein C) during simulated Y-site administration with drugs commonly used to treat patients with severe sepsis was determined. METHODS: Thirty-four drugs were investigated for visual compatibility with drotrecogin alfa, and included cardiovascular agents, conscious sedative agents, antibiotics, blood products, and other supportive care drugs. The physical and chemical compatibility of drotrecogin alfa with these drugs was determined using a well-established experimental model to simulate Y-site administration. Drotrecogin alfa (activated) was prepared as 100- and 1000-microg/mL solutions in 0.9% sodium chloride injection. All other drugs were prepared at maximum concentrations commonly administered in the clinical setting. Visual compatibility was assessed by visual inspection (observations of haziness, color change, or precipitate formation) and pH measurement at 0, 30, 60, and 240 minutes after mixing. RESULTS: Of the 34 test drugs, 8 were defined as visually compatible with drotrecogin alfa; these drugs were further assessed for chemical compatibility with drotrecogin alfa. The protein content, potency, and purity of drotrecogin alfa were determined at 0, 60, and 240 minutes after Y-site mixing as indicators of chemical compatibility. Six drugs (ceftriaxone, cisatracurium, fluconazole, nitroglycerin, potassium chloride, and vasopressin) were determined to be chemically compatible with drotrecogin alfa; two drugs (cyclosporine and ticarcillin-clavulanate) were chemically incompatible with drotrecogin alfa after Y-site mixing. CONCLUSION: Ceftriaxone, cisatracurium, fluconazole, nitroglycerin, potassium chloride, and vasopressin were physically and chemically compatible with drotrecogin alfa in a simulated Y-site infusion; 28 other drugs were incompatible with drotrecogin alfa.

In vitro characterization of oritavancin clearance from human blood by low-flux, high-flux, and continuous renal replacement therapy dialyzers.

BACKGROUND: Oritavancin is an investigational lipoglycopeptide antibiotic under clinical development for the treatment of gram-positive bacterial infections. The impact of hemodialysis on plasma concentrations of oritavancin is unknown and may be important in making dosage adjustments in such patients. The present study sought to determine the clearance of oritavancin from human blood by various commercially available dialyzers in an in vitro hemodialysis model. METHODS: Three types each of low-flux (Dicea 130, F6, and Polyflux 14L) and high-flux (Revaclear, Exeltra 150, and Optiflux F160NR) dialyzers and one type of continuous renal replacement therapy (CRRT) dialyzer (Prismaflex M100) were studied. Heparinized human blood containing oritavancin (200 mg/L) was circulated from a reservoir to the dialyzers and back to the reservoir. Fresh dialysate was pumped through the dialyzers in a countercurrent manner. Blood samples from each side of the dialyzers and contaminated dialysate samples were collected at periodic intervals. Oritavancin levels were analyzed by a liquid chromatography/mass spectrometry method with a limit of quantification of 12.5 ng/mL and plasma clearances of oritavancin were calculated. RESULTS: The mean dialytic clearance of oritavancin was insignificant for each of the low-flux, high-flux and CRRT dialyzers. Clinically significant amounts of oritavancin were not detected in dialysate during any of the experimental dialysis sessions. CONCLUSIONS: The clearance of oritavancin from human blood by the dialyzers used in this study is insignificant. Further clinical studies would be required before making changes in dosage of oritavancin in hemodialysis patients.

Visual compatibility of oritavancin diphosphate with selected coadministered drugs during simulated Y-site administration.

PURPOSE: The visual compatibility of the new intravenous antibiotic oritavancin diphosphate with various drugs commonly administered to patients in acute care settings was studied. METHODS: Clinically used concentrations of 37 drugs, including antibiotics, sedatives, analgesics, and cardiovascular agents, were evaluated in 1:1 mixtures with oritavancin concentrations of 0.8, 1.2, and 2 mg/mL. Oritavancin solutions were prepared in 5% dextrose injection and mixed with each test drug solution. The mixtures were then visually observed over a period of four hours at room temperature. The pH of the mixtures was also determined immediately and four hours after mixing. Compatibility was defined as the absence of any color change, haze, fibers, particles, and precipitate. RESULTS: Of the 37 tested drugs, 23 were visually compatible with all three concentrations of oritavancin over the four-hour study period. Drugs formulated at a basic or neutral pH were more likely to be incompatible with oritavancin. CONCLUSION: Oritavancin diphosphate was visually incompatible with many intravenous drugs that are likely to be coadministered in acute care settings.

Cooperation in pharmacy education in Canada and the United States.

Although the education of student pharmacists and the practice of pharmacy in Canada have many similarities with that in the United States, there also are differences. The planning of curricula in pharmacy education is of particular importance to the advancement of pharmacy in Canada because of significant changes in the scope of practice in several provinces, and in how community pharmacy is reimbursed for the services it can, or should, provide. Greater dialog between Canadian and American pharmacists has the potential not only to impact practice on both sides of the border but also to improve collaborations among Canadian and American pharmacy educators. This article provides background information and some suggestions on how to build partnerships in pharmacy education between Canada and the United States. Consortia-like arrangements have some particular promise, as does engaging border-states and provinces in regional meetings and other activities. By working together, Canadian and US pharmacy educators have the opportunity to implement the best of what each has to offer and to devise new and better ways to educate future and existing pharmacists.

Inadequate antibiotic therapy in solid organ transplant recipients is associated with a higher mortality rate.

BACKGROUND: Inadequate antibiotic therapy and failure to administer antibiotics in a timely fashion have been associated with substantial mortality rates in patients in the intensive care unit (ICU). We analyzed the infection pattern in solid organ transplant recipients as well as the impact of antibiotic resistance and inadequate antibiotic treatment on mortality rates and morbidity outcomes. METHODS: Charts of adult solid organ transplant recipients in 2006 from a single institution were reviewed. Data on patients with bacterial and fungal infections acquired within one year after transplantation were compared with the primary outcome of death within 28 days. Statistical analysis included nonparametric tests (Wilcoxon rank sum, Fisher exact, and chi-square) and multivariable logistic regression with p < 0.05 considered significant. RESULTS: Of the 366 patients, 114 (31%) had a total of 208 bacterial or fungal infections, and 44 of them (39%) were admitted to the ICU. Our primary endpoint, the 28-day mortality rate, was 8% overall, whereas the six-month mortality rate was 11%. Patients treated inadequately with antibiotics had a significantly higher mortality rate. The leading causes of infection were multiple organisms, coagulase-negative Staphylococcus, and E. coli, of which 76% were resistant to antibiotics. Antibiotic-resistant infections were associated with longer hospital stays (p = 0.04), intravenous antibiotic use prior to infection (p = 0.04), nucleotide synthesis inhibitor use (p = 0.02), ICU admission (p < 0.01), and respiratory failure (p = 0.03). Most infections were treated inadequately initially (69%) but treated adequately at 24 h (56%). Inadequate antibiotic treatment was significantly associated with younger age (p = 0.04), prior intravenous antibiotic use (p = 0.04), longer stay prior to infection (p = 0.05), and cardiovascular shock (p = 0.014). Inadequate antibiotic therapy at 24 h was associated with a higher mortality rate (14% vs. 2%; p = 0.03) and a trend toward longer ICU and in-hospital stays. CONCLUSIONS: Most bacterial and fungal infections were resistant to antibiotics and were treated inadequately initially. Prior intravenous antibiotic use and longer stay prior to infection were associated with antibiotic resistance and inadequate antibiotic therapy. Failure to provide adequate antibiotic treatment within 24 h had a significant impact on the 28-day mortality rate and was associated with other detrimental clinical outcomes.