Christopher W. Crank

Bio: Christopher W. Crank is an academic researcher from Rush University Medical Center. The author has contributed to research in topics: Daptomycin & Vancomycin. The author has an hindex of 19, co-authored 26 publications receiving 1411 citations. Previous affiliations of Christopher W. Crank include The American College of Financial Services.

Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management.

Abstract: Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.

Clinical Pharmacist Competencies

Abstract: The American College of Clinical Pharmacy (ACCP) strategic plan summarizes its core ideology, envisioned future, core purpose and mission, and critical issues for the organization and the profession. A longstanding critical issue of the college’s plan is how ACCP can contribute to ensuring an appropriately educated and skilled clinical pharmacy workforce. Toward that end, the college sought to publish a definition of clinical pharmacy and establish the competencies of a clinical pharmacist. Coincident with the development of its definition of clinical pharmacy, the ACCP Board of Regents charged a task force to develop a complete set of competency statements for the clinical pharmacist. These statements were to be assessable and able to serve as a foundation for the development of future clinical pharmacist assessment tools. In developing the competency statements for this paper, the authors reviewed a number of documents that addressed competencies within the profession of pharmacy, including the Accreditation Council for Pharmacy Education (ACPE) Accreditation Standards for the Doctor of Pharmacy degree, the American Association of Colleges of Pharmacy (AACP) Center for the Advancement of Pharmaceutical Education (CAPE) Education Outcomes, the American Society of Health-System Pharmacists (ASHP) and ACCP joint statement on learning objectives for residency training in pharmacotherapy, and the Board of Pharmaceutical Specialties content outline for the Pharmacotherapy Specialty Certification examination. Consensus competencies of a clinical pharmacist were identified. Draft competencies and associated content knowledge components were then prepared for review by the ACCP Board of Regents. After extensive deliberations, the authors identified key differences between the competencies of a clinical pharmacist and today’s pharmacy generalist.

High-Dose Daptomycin for Treatment of Complicated Gram-Positive Infections: A Large, Multicenter, Retrospective Study

Abstract: Study objective To evaluate the clinical response and safety of high-dose daptomycin for treatment of complicated gram-positive infections. Design Multicenter, retrospective, observational, case series analysis. Setting Five academic medical centers in four major United States cities. Patients Two hundred fifty adults, not undergoing dialysis, who received high-dose daptomycin (≥ 8 mg/kg/day) for at least 72 hours for complicated gram-positive infections between January 1, 2005, and March 1, 2010. Measurements and main results Clinical and microbiologic outcomes were assessed at the end of high-dose daptomycin therapy. Safety evaluations were recorded for all patients, and when available, baseline, end-of-therapy, and highest observed serum creatine phosphokinase (CPK) levels were recorded. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) were the primary organisms isolated. The median dose of daptomycin was 8.9 mg/kg/day (interquartile range [IQR] 8.0-10.0 mg/kg/day). The median duration of daptomycin during hospitalization for MRSA and VRE infection was 10 days (IQR 5-16 days) and 13 days (IQR 6-18 days), respectively. Among the 250 patients, high-dose daptomycin was primarily used as salvage therapy after vancomycin treatment (184 patients [73.6%]). Primary infections included complicated bacteremia (119 patients [47.6%]), endocarditis (59 [23.6%]), skin or wound (70 [28.0%]), and bone or joint (67 [26.8%]). Overall, clinical response and microbiologic success were assessed in 83.6% (209/250 patients) and 80.3% (175/218 patients), respectively. Isolates from 13 patients (5.2%) developed nonsusceptibility to daptomycin, with most of these patients having extended vancomycin exposure. Three patients (1.2%) developed an adverse event attributable to high-dose daptomycin therapy, with the event considered either mild or moderate in severity. The median end-of-therapy CPK level was 39 U/L (IQR 26-67 U/L). No significant correlation was found between daptomycin dose and highest observed CPK level. Conclusion Daptomycin dosages of 8 mg/kg/day or greater may be safe and effective in patients with complicated gram-positive infections. Further clinical studies are warranted.

A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis

Abstract: Objectives Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of high-dose daptomycin, defined as ≥8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE.

Daptomycin for the Treatment of Gram-Positive Bacteremia and Infective Endocarditis: A Retrospective Case Series of 31 Patients

Abstract: Study Objective. To evaluate the outcomes in patients with bacteremia and/or infective endocarditis who were treated with daptomycin. Design. Retrospective chart review. Setting. A university-affiliated medical center in Chicago, Illinois, and a regional hospital in Fountain Valley, California. Patients. Thirty-one inpatients treated with daptomycin for bacteremia and/or infective endocarditis. Measurements and Main Results. Patients were given daptomycin 4–6 mg/kg intravenously every 24–48 hours based on the practitioner's discretion and depending on the patient's clinical condition and presence of comorbidities. Primary end points were resolution of signs and symptoms of infection and discharge from the hospital. Methicillin-resistant Staphylococcus aureus ([MRSA] 11 patients) and vancomycin-resistant entercocci ([VRE] 11 patients) were the most common pathogens, whereas 7 patients had methicillin-sensitive S. aureus infection and 1 patient had coagulase-negative Staphylococcus infection. One patient with endocarditis had a negative culture result. Overall, 24 (77%) of the 31 patients achieved clinical resolution and were discharged, including all patients infected with MRSA; 7 patients died, 6 of whom had VRE infection. Duration of treatment for infective endocarditis lasted longer (typically 22–43 days) than that for bacteremia only (≤ 14 days), and no patients discontinued daptomycin because of adverse events. Conclusion. In these patients, daptomycin was safe and well tolerated even for extended durations of treatment. Daptomycin may provide an effective option for treating drug-resistant gram-positive bloodstream infections and endocarditis.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

Abstract: Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

Abstract: To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao 2/Fio 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao 2/Fi o 2 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America

Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.

2015 ESC Guidelines for the management of infective endocarditis

Abstract: 3D : three-dimensional AIDS : acquired immune deficiency syndrome b.i.d. : bis in die (twice daily) BCNIE : blood culture-negative infective endocarditis CDRIE : cardiac device-related infective endocarditis CHD : congenital heart disease CIED : cardiac implantable electronic device

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

Abstract: Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.