POTENTIAL FOR REGIONAL COLLABORATION MARK E. DOWELL, MD FACP ROCKY MOUNTAIN INFECTIOUS DISEASES Antibiotic Stewardship Programs

ASP 1998: Institute of Medicine. Annual cost of infections caused by antimicrobial- resistant bacteria: $4-$5 billion.

ASP Antimicrobials may constitute up to 30% of hospital pharmacy budget.

ASP Up to 50% of antimicrobial use is inappropriate.

ASP Resistant Organisms Methicillin-resistant Staphylococcus aureus (MRSA) Vancomycin-resistant Enterococcus (VRE) Clostridium difficile (C. diff.) Extended-spectrum beta-lactamase (ESBL) Carbapenem-resistant Enterobacteriaceae (CRE)

ASP MRSA Bacteremia or surgical site infection:  $9,275-$13,901 VRE Bacteremia:  30% excess mortality vs. sensitive Enterococcus.  Doubled LOS, $27,190 additional cost.

Staphylococcus aureus Bacteremia $20, $70, per episode. MRSA increases length of stay and cost fold when compared to MSSA. MSSA mortality higher if treated with vancomycin.

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ASP CID 2008: 46: Background  University of Colorado 2005 policy mandatory infectious disease consultation for Staph aureus bacteremia.  4 key management elements:  A.) Removal of intravascular device (if a focus), within 4 days.  B.) Follow-up blood cultures days 2-4.  C.) Use of beta-lactam antibiotics for MSSA.  D.) Administration of minimum 28 day treatment course.

Conclusions 72% bedside consultation, 18% telephone, 10% none. Bedside led to identification of deep foci. Bedside led to decreased mortality at days 7, 28, day mortality for telephone odds ratio 2.31.

Case Study A 57 year old male presents with fever, chills, and confusion. There is nothing remarkable in his history in discussion with his family. He is febrile and tachycardic, but physical examination is nonspecific. The WBC count is 18,000 with mild left shift. Chest radiograph and urinalysis normal. Blood cultures are drawn and he is empirically started on piperacillin-tazobactam and vancomycin.

Day 2 Approximately 18 hours later, all 4 blood culture bottles are growing gram-positive bacteria upon gram-staining. There are no changes made to the antibiotic regimen.

Day 3 The next morning on rounds, the report on the computer says “gram positive growth, presumptive staph.” No changes are made.

Day 4 Another day passes, and on rounds the report does not show finalized identification and sensitivities. “Zosyn” and vancomycin are continued.

Day 5 The next morning, during rounds, the final report is noted, revealing MSSA. The “Zosyn” is discontinued. A vancomycin trough is 10.

DAY 5 LATE The patient remains ill and on Day 5, in the evening, The infectious disease service is consulted.

DAY 6 AND ONWARD Repeat blood cultures are drawn and the patient is switched to nafcillin. Infectious disease work up finds mitral valve infective endocarditis.

ASP OPTIMIZE:  Antimicrobial selection  Dosing  Route of administration  Duration

ASP Begins with:  Collaboration between infectious diseases physician, pharmacy champion, and infection control. Requires buy in from:  Administration.  Medical staff leadership.  Local providers.

ASP Programs must be adapted to resources available. Beginning a program is cost-effective and quickly saves money for even small facilities.

ASP In smaller rural hospitals, challenges may be met:  Collaboration with larger institutions (protocols).  Contracting with Infectious Diseases physicians.  “Outside” education.

ASP Important Components Basic provider knowledge about antibiotics. Extensive use of Infectious Diseases consultation. Detail about antibiotic “allergies” for a given patient. Hospitalist programs, vs. local provider hospital care. Non-threatening advice.

ASP Broad education (lectures, s, etc.) help for a brief period. BUT Long term changes occur with colleague-to-colleague interactions plus standardized interventions.

ASP The ability to track antimicrobial prescribing practices utilizing EMR may result in dissemination of valuable information that could be utilized for standardization and education.

ASP Must find correct balance between interventions and development of resentment.

ASP Key components include the accuracy of diagnosis and ability to interpret microbiologic data.

Antimicrobial Cycling An attempt at controlled heterogeneity of antimicrobial use to minimize antimicrobial selection pressures. In theory, should be effective. Tough to evaluate in studies. Requires strong infectious disease presence or infection control- trained pharmacy team.

ASP Cycling may not reduce evolution or spread of resistance but may slow the spread (resistance).

ASP National guidelines must not supercede local quality patient care that is based upon regional population and resistance patterns.

ASP De-escalation. Dose optimization.

ASP The much muted pharmaceutical representative presence and influence will play a significant role in the spectrum of ASP, especially in the outpatient setting.

Case Study 2 A 68 year old woman is admitted for an exacerbation of congestive heart failure. A Foley catheter is inserted to monitor urine output. On day 3, the nurse notifies the provider that the urine is cloudy.  What question(s) do you ask?  What tests to you order?  What interventions do you start?

Case Study 2 continued The patient’s vital signs are stable. A CBC reveals a WBC count of 10,000. A urinalysis displays large leukocyte esterase, nitrite positivity, and packed fields of wbc and bacteria.

Case Study 2 continued Levafloxacin is ordered (intravenous).

Case Study 2 continued The urine culture reveals E.coli, resistant to ampicillin, ampicillin-sulbactam, and sulfa.

Case Study 2 continued The levafloxacin, after 3 days, is converted to oral to complete a 7 day total course.

Case Study 2 continued At the end of treatment, the urine has sediment, the patient has not clinically changed, and her WBC count is 9,000.

ASP Train providers not to culture. If culture, train to understand results and to not use antibiotics. If patients symptomatic (true infection), treat and narrow spectrum of antibiotic ASAP.

Inappropriate treatment of symptomatic bacteruria occurs in up to one half of catheterized patients.

ASP Wyoming Medical Center Restriction of some antimicrobials. Strong role of pharmacy. Selective antimicrobial sensitivity reporting. Strong collaboration between ID team, pharmacy, infection control, employee health, and the emergency room. Ongoing broad and individual education in hospital and outpatient arena including antibiograms. Strong ID presence.

Restricted Antimicrobials - WMC Linezolid Daptomycin Cefepime Ertapenem Meropenem Tigecycline Micafungin Liposomal amphotericin

IV  PO Conversion Benefits Lower cost. Lower catheter-related infections. Shorter length of stay. Decreased workload.

Examples of IV  PO substitution Fluoroquinolones Clindamycin Metronidazole Fluconazole Sulfa-based drugs Linezolid

IV  PO Conversion Johns Hopkins: voriconazole, pantoprazole, chlorothiazide, levetiracetam. More than 67% patients were on IV formulation despite oral intake. This added $1.1 million to the direct cost annually.

IV  PO Conversion VA system:  47% of all quinolone days were avoidable IV days. Potential Savings: $4 million.

Oral Vancomycin – Ohio State University System Form  Capsule  Liquid Cost  $23.42/125mg dose  $0.94/125mg dose Potential Annual Savings: $218,877

ASP Undefined Factors Aging Intervention-related immunosuppression Immunosenescence

ASP Yet to be determined Role of office prescribing patterns on community- wide resistance in bacteria. Role of LTCF prescribing habits. Role of food animal antimicrobial use.

ASP Well designed, comprehensive programs can decrease antibiotic use 22%-36% with an annual savings of $200,000 - $900,000.

2007 An episode of MRSA bacteremia or major surgical site infection will add $9, to $13, to the cost of care.