ANti-infective Stewardship Using the Wisca Tool in the Electronic Medical Record

The decade of the 1970s was a time when the PI was completing his training and beginning a
career in Infectious Diseases and Microbiology. This was an era when many new anti-infective
compounds were being introduced, ranging from novel penicillins to extended-spectrum
cephalosporins to aminoglycosides. The main antimicrobial resistance concern at the time was
Staphylococcus aureus that was no longer susceptible to penicillin; methicillin, oxacillin,
and nafcillin had solved that problem. Even for those strains that later were
methicillin-resistant (MRSA), vancomycin had been available since the 1950s. Later the
carbapenems and in the 1980s the newer fluoroquinolones, beginning with ciprofloxacin, were
introduced for clinical use. At the time it seemed that the challenge of treating serious
infection in humans had been met and that other diseases were a higher priority. Indeed, in
1978 one of the world's leaders in infectious diseases, Dr. Robert Petersdorf, commented that
"Even with my great personal loyalty to Infectious Disease, I cannot conceive of the need for
309 more [graduating trainees in] infectious disease...unless they spend their time culturing
each other". However, in Alexander Fleming's 1945 Nobel prize lecture he warned of the danger
of antimicrobial resistance stating "it is not difficult to make microbes resistant to
penicillin in the laboratory by exposing them to concentrations not sufficient to kill them,
and the same thing has occurred occasionally happen in the body . . . and by exposing (his)
microbes to nonlethal quantities of the drug make them resistant". It was also at this time
that Infection Control began as an established discipline with CDC offering the first course
in 1968 and the Joint Commission requiring a hospital position for Infection Control in 1969.
Subsequently, beginning in the mid-to late 1980s and accelerating through the 1990s and 2000s
the shield of antibiotic invincibility began to crack sufficiently so that it was apparent to
everyone we faced a serious problem. Resistance began to be reported in Gram negative
bacteria toward the newer cephalosporin, fluoroquinolone, and even the carbapenem drugs.
During this same period modern medicine witnessed the emergence and spread of a new
healthcare associated infection called Clostridium difficile associated diarrhea, as well as
MRSA becoming pandemic. It was during this time that the initial studies focused on reversing
antimicrobial resistance began. In fact, Drs. Dale Gerding and Lance Peterson undertook the
first ever antibiotic cycling program using amikacin and gentamicin to demonstrate that
withdrawal of an antibiotic to which resistance had developed would restore the activity of
that drug. Humanity now faces a healthcare setting where as many as 70% of the bacterial
infections afflicting patients are resistant to at least one antimicrobial that was initially
active against historical bacterial ancestors. In a sense, the investigators have been
preparing for this funding announcement for nearly an entire career - and are confident that
the investigators can 'answer' the challenge of reversing antibacterial resistance and
reducing that threat for healthcare-associated infections (HAIs). The objectives are in the
main area that describes the focus for this application, which is Antimicrobial Stewardship:
Preventing the development and spread of resistant organisms in the healthcare setting.

There are two specific aims for this research program to accomplish. They are:

1. Specific Aim 1: Complete development of the personalized weighted-incidence, syndromic,
combination antibiogram (WISCA) tool and validate its performance as a comprehensive
strategy to improve the treatment of infectious diseases for all hospitalized patients.

- The investigators will demonstrate and expand the use of information technology based
on the WISCA for the widespread use of automated clinician prompts enhancing empiric
antibiotic therapy as part of a comprehensive infection control stewardship program that
reduces antibiotic resistance.

2. Specific Aim 2: Demonstrate that use of such a tool improves patient outcome, lowers
antimicrobial resistance and reduces cost.

- The clinical and economic outcome measures will include changes in length of stay,
duration of treatment, use of therapeutic drug monitoring, inpatient mortality,
adverse events from antibacterial therapy, admission and discharge location (with
the goal being fewer persons needing skilled care after discharge than is now
required), 30 day readmission rates, unintended consequences from antimicrobial
agent use, such as Clostridium difficile infection, antimicrobial drug cost and
antimicrobial susceptibility.

All the investigator faculty are well aware of current developments in the relevant fields
and are actively involved in cutting edge research that will be applied in a comprehensive,
integrated fashion to solve the problem of antimicrobial resistant HAIs. The investigators
look forward to working on this Large Research Project with the Agency for Healthcare
Research and Quality for the improvement in the care of United States citizens.

Inclusion Criteria:

- Any person admitted to the hospital with pneumonia, cellulitis, intraabdominal
infection, or urinary tract infection

Exclusion Criteria:

- Any person without the 4 studied infections