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CAUSE Projects and Research

The following are brief summaries of various CAUSE initiatives that are anticipated to improve quality and/or reduce or avoid costs.

Micafungin for antifungal treatment of neutropenic fever

Caspofungin is an acceptable option as empiric antifungal treatment of neutropenic fever. A randomized, controlled clinical trial documented its success for this indication. However, the WFBMC formulary includes micafungin, a very similar echinocandin antifungal. Studies of micafungin describe efficacy similar to caspofungin for other indications, and pharmacological properties of micafungin are essentially the same as caspofungin. For this reason, CAUSE staff members elected to extrapolate and use micafungin as empiric antifungal treatment of neutropenic fever. To validate this decision, CAUSE staff members studied the efficacy of micafungin for this indication as compared with similar patients who received amphotericin B lipid complex, a historical gold standard. The results of the study showed equivalent efficacy and a better safety profile of micafungin.

Pneumonia antibiotics order set

A six sigma project was initiated to improve the time to antibiotic administration for direct admit patients with pneumonia. A “pneumonia antibiotics order set” was developed by CAUSE staff as a key ingredient in the process for improving timeliness and choice of antibiotics. Although it was intended for direct admits, the applicability was revised and extended to all patients, including those who develop hospital-acquired pneumonia and those who are critically ill. The order set is novel in that it utilizes two variables to provide clinical decision support in prescribing antibiotics for pneumonia. The order set was converted into order entry screens in CareCast, and the screens were designed to serve as a tool for capturing disease indications that may be used by hospital coders. The screens were vetted and approved by the Physician Tailoring Team, and use of the order set has been promoted through inservices to house staff.

Analysis of carbapenem MICs

An additional carbapenem, doripenem, was recently approved by the FDA.  CAUSE staff members identified potential clinical and economic advantages of changing the WFBMC formulary anti-Pseudomonas carbapenem from meropenem to doripenem. During the review, these advantages were found to be dependent on what dose of doripenem is prescribed. CAUSE completed an analysis of 60 Pseudomonas isolates to compare the MICs among the carbapenems currently on the market. This analysis helped determine the optimal dosing of doripenem and supported a change to doripenem as the preferred anti-Pseudomonas carbapenem at WFBMC.

Vancomycin dosing optimization

Vancomycin serum concentration monitoring has been available for decades to help clinicians individualize dosing.  Emerging evidence correlating patient-specific vancomycin exposure with effectiveness and toxicity led to the publication of collaborative guidelines on therapeutic monitoring of this agent in adults (Rybak, et al, Am J Health-Syst Pharm 2009;66:82, Clin Infect Dis 2009;49:325).   Working with Pharmacy Information support, CAUSE staff developed special CareCast CPOE guidance screens and updated pocket dosage cards to reflect these changes, assisting clinicians in the optimal use of this antimicrobial.

Education of Internal Medicine and Family Practice Residents

Over the course of two years, the CAUSE staff completed an educational intervention with internal medicine and family practice residents (PGYs 1-3). The intervention consisted of a monthly one-hour conference that focused on antimicrobial stewardship issues. The conferences used a case-based format to highlight common areas of inappropriate antimicrobial use, as identified by CAUSE staff through ID consult rounds, the CAUSE pager, or AST rounds. The CAUSE staff members served as an "expert panel" for the residents and provided feedback on cases presented by the residents. Also, residents brought questions to the conference and participated in a Q & A session with the CAUSE staff in order to achieve a better understanding of infectious diseases and appropriate antimicrobial use. Common errors in clinical reasoning with regard to appropriate antibiotic use were addressed in the conference. The residents completed a pre-test and post-test in order to determine whether their knowledge and clinical reasoning skills improved after attending the conference series. Further, residents completed a self-assessment to critically appraise their decision-making after they had presented a case. The residents were evaluated by faculty and received verbal feedback on their medical decision making involved in the case. Formative evaluations from the residents were very favorable with the majority of respondents indicating that the conference adequately prepared them to select antimicrobial therapy and to select appropriate diagnostic studies in order to streamline or de-escalate antimicrobial therapy. The majority of respondents also indicated that they feel well prepared to discontinue and/or withhold antimicrobial therapy where appropriate, interpret susceptibility testing on resistant bacteria, and self-assess and engage in practice-based learning as a result of the conference.

Prospective Review of CAUSE Prior Authorization/Restriction (PA) encounters with Health Care Providers

For each PA encounter from Nov 2008-Jan 2009 data was collected by CAUSE team members that included requesting service, training level of caller, attending MD, geographic patient location, requested antimicrobial, reason for request, infection history of the patient, and PA recommendation. 257 PA encounters were recorded during the 3 month period. 105 (41%), 73 (28%), and 61 (24%) were from hematology/oncology, ICU, and general medicine services respectively. 75% of interactions were with upper level residents and interns. Requests for restricted antimicrobials accounted for 89% of encounters and general antimicrobial advice for the remainder. The most commonly requested restricted drugs were carbapenems (76), voriconazole (50), daptomycin (34), linezolid (20), and echinocandins (12). 81% of requested drugs were approved, while 19% were disapproved with recommendations made for de-escalation or a different drug. The median interaction time was 6 min (range 2-60 min). In 3 patients the approval process resulted in a delay in antimicrobial administration of 1-2 hours. Collection of this PA encounter data was a useful process measure and was used to target antimicrobial education and intervention and provided a snapshot of an important activity of CAUSE. PA seldom delayed antimicrobial administration. These results were published in abstract form and presented at the annual Infectious Diseases Society of America Meeting in the fall of 2009.

Update of antibiotic information in operating room computer software

The operating suite uses a specialized computer software system often referred to as John Galt. The software has the ability to guide surgeons and anesthesiologists on the use of perioperative antibiotics, based upon the unique information placed in the system by the hospital’s designated informatics representative. CAUSE staff members are working with the Quality Resource Center to maximize the utility of John Galt by providing antimicrobial content. Such information will ensure appropriate choice and timing of perioperative antibiotics and help satisfy CMS-mandated core measures related to surgical prophylaxis.

Clinical efficacy of colistin alone or in combination with beta-lactam antibiotics

Increasing rates of resistance among gram-negative bacilli (GNB) has led to the reassessment of colistin’s clinical utility. Compared with colistin alone, in-vitro time-kill studies have demonstrated improved microbiological activity when colistin is used in combination with beta-lactam antibiotics. However, a lack of data exists to validate the clinical efficacy of these combinations. Therefore, CAUSE staff members retrospectively compared the clinical efficacy of colistin when used alone or in combination with a beta-lactam antibiotic for the treatment of infections caused by multidrug-resistant GNB. Combination therapy produced a higher rate of clinical efficacy and lower rate of superinfections due to innately colistin resistant bacteria. Manuscript preparation is underway.

Analysis of monitoring vancomycin concentrations at WFBMC

Effective therapeutic drug monitoring (TDM) is essential to optimize therapeutic plasma vancomycin concentrations for increasing clinical outcomes, while decreasing resistant microorganisms and adverse drug reactions.  In 2009 the Infectious Diseases Society of America (IDSA), the American Society of Health-System Pharmacists (ASHP), and the Society of Infectious Disease Pharmacists (SIDP) released consensus guidelines pertaining to therapeutic monitoring of vancomycin in adult patients.  These guidelines, based on literature review and expert opinion, outline appropriate methods for monitoring vancomycin, including specific strategies for TDM. CAUSE team members analyzed a month’s worth of vancomycin concentrations at WFBMC for appropriateness. The analysis discovered areas for improvement in the way vancomycin concentrations are obtained, particularly with regard to timing and interpretation of the levels. These results will be presented at the Pharmacy and Therapeutics Committee meeting and a process improvement plan will be developed in late 2010.

Mupirocin for MRSA decolonization

In collaboration with Department of Infection Control, CAUSE clinicians worked to develop pharmacologic aspects of a comprehensive approach to reduce healthcare associated infections due to methicillin-resistant Staphylococcus aureus (MRSA).   Following principles from published evidence of benefit from such a program, a protocol for nasal application of mupirocin ointment was developed as part of a strategy to eliminate colonization by this organism, and prevent infections.   Patients identified on nasal screening to be colonized with MRSA will undergo decolonization therapy with intranasal mupirocin ointment.   Daily neck-down baths with a chlorhexidine-impregnated washcloth, once instituted for all ICU patients, will aid this intervention.   The impact on the incidence of nosocomial MRSA infection will be monitored.   During the development of this program, CAUSE team members worked to assure the quality and safety of a switch from budgeted Bactroban Nasal to generic topical mupirocin ointment.

Empiric antibiotic selection in beta-lactam allergic pts

Numerous studies have demonstrated the importance of initiating appropriate empiric antibiotic therapy.  Consideration of local microbiologic data is essential in developing institution-specific recommendations for that therapy.  ß-lactams (penicillins, cephalosporins, carbapenems) are frequently drugs of choice in community- or hospital-acquired infections.   However, few data exist to guide prescribers in antibiotic selection for patients with severe ß-lactam allergy.  Declining reliability of several non-ß-lactam antibiotic agents over the past decade against gram-negative bacterial pathogens prompted the initiation of an IRB-approved retrospective investigation of this question.   In this study, the bacteriology and susceptibility of clinical infections in patients with beta-lactam allergy were examined to determine optimal antibiotics or combinations for use in several commonly encountered scenarios. Results of this study were presented in poster format at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in September 2010.


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Christopher Ohl, MD
CAUSE Medical Director

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Last Updated: 08-30-2016
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