Outpatient Parenteral Antibiotic Therapy Katie Sheridan, DOMedical Director, OPAT Program UPMC Presbyterian CampusClinical Associate Professor of Medicine, Department of Medicine Division of Infectious Disease

Objectives› Define OPAT› Discuss OPAT in special populations› Discuss OPAT Program at PUH› OPAT Alternatives

What is OPAT? › Administration of parenteral antibiotics in a non-hospital

setting of at least 2 doses on different days› Established in United States since 1974

› Primary goal is to allow patients to complete safe & efficacious antibiotic courses in their home or an outpatient setting– Also prevents potential exposures to HAIs, reduce inconvenience to

patients, decrease cost of hospitalization

Efficacy of OPAT› First shown efficacious in treatment of chronic

bronchopulmonary infections in children with cystic fibrosis› Shown efficacious for the treatment of various types of

infections including but not limited to cellulitis, osteomyelitis, prosthetic joint infections, endocarditis, pyelonephritis and others

› Also demonstrated efficacious with various antibiotics› Can be administered in various settings including home,

infusion center, physician office, skilled nursing facility

Considerations for patient selection/disposition› Medical/Physical limitations › Insurance› Caregiver› Home environment

Antibiotic considerations› PK/PD › Bioavailability/Tissue penetration› Dosing schedule

Antimicrobial Pharmacodynamics

Antibiotics that can be administered as continuous infusion› Ampicillin*› Ampicillin/sulbactam*› Penicillin› Oxacillin/Nafcillin› Piperacillin-Tazobactam› Cefazolin

Antibiotics administered once daily› Ceftriaxone› Ertapenem› Moxifloxacin› Levofloxacin› Daptomycin› Gentamicin› Amikacin› Fluconazole› Caspofungin› Amphoptericin› Dalbavancin/Oritvancin*

Oral Bioavailability

Hydrophilic vs Lipophilic Agents

Monitoring while on OPAT› Evaluate for response to therapy› Therapeutic drug monitoring› Monitor for antibiotic associated adverse event› Monitor for new HAI› Monitor for vascular device associated complications› Ongoing review for drug-drug interactions› Ensure appropriate completion of antibiotic course

OPAT eHandbook IDSA

OPAT in Special PopulationsPWIDElderly patients

OPAT in PWID › Retrospective review of PWID

discharged from PUH 2013 to 2015

› OPAT Failure defined as ANY of the following:– Worsening or ongoing infection

requiring hospital readmission within 30 days

– Worsening or ongoing infection at office follow-up resulting in extension of therapy

– Premature discontinuation of OPAT

– Patient noncompliance– Death during treatment

› 91% of patients had a single organism with Staph Aureus being the most common

Diagnosis & Antibiotic Utilization

Risk Factors for OPAT Failure

› Of PWID enrolled in OPAT, 61% (41/67) failed OPAT

› Age, discharge location, diagnosis, pathogen isolated, drug choice, adverse event to antibiotic, and non-adherence to ID follow-up were not risks for OPAT failure

› Median time since last IVDU was shorter among patients who failed versus completed OPAT (3 weeks vs 8 weeks; P=0.02)

› By multivariate analysis, time since last IVDU was independently associated with OPAT failure (P=0.04)

Buehrle et al Open Forum Inf Dis 2017

OPAT in PWID at other sites› Review of Literature ~ 10 publications. 6 in US, 2 in Canada, 1 in Australia

and 1 in Singapore› Mainly Bone/joint infections 38%, Endocarditis 21%, SSTI 16%,

Bacteremia 7%› Mainly males with recent injection use within 4 weeks› OPAT completion rates ranged from 72-100% with duration of 18 to 42

days› OPAT non-adherence ranged from 1 to 36%› Mortality rates range from 0-10%› Venous access complications ranged from 2.7 to 9.4%› 1 study reported on drug relapse rate within 12 months: 40% among

“high risk”, 20 %in “medium risk” and no relapse in “low risk”

Suzuki et al Open Forum Inf Dis 2018

OPAT in the Elderly› Retrospective review from 2015 to 2018 of patients discharged from PUH, MUH, or Magee on

OPAT to compare 30 day readmission rates for patients aged >/= 80 or < 80 years of age

› Patients could be discharged to home, SNF/IPR or LTAC though patients > 80 were more likely to be discharged to a facility

› More comorbidities were observed in the >80 cohort

› Staph Aureus was the most common organism with vancomycin being the most commonly used antibiotic

Sheridan et al IDWeek 2019

OPAT in the Elderly at Other Sites

› Yale: patients > 65 did not have increased healthcare utilization compared to patients < 651

› Cleveland Clinic: Similar rates of ER visits, readmissions in > 90 years old & younger matched cohorts2

1 Datta et al IDWeek 2018 2 Blaskewicz et al IDWeek 2018

OPAT at UPMC

Background› OPAT Program at PUH/MUH & Magee began in December

2013› Baseline 30 day readmission rate for patients discharged on an

IV antibiotic was 32% compared to 25% for the general population

› Developed to reduce 30 day readmission rates, number of ER visits and prevent antibiotic associated adverse events

Background: CCID OPAT Program

= Addition of a Hospital. Northwest in 2014, Jameson, Horizon & Shadyside TID added in 2018

OPAT Goals

Evaluate Evaluate patients in the outpatient ID clinic within 7-14 days post discharge and prior to completion of IV course

Ensure Ensure better laboratory monitoring of patients to identify potential issues

Identify Proactively identify potential adverse events related to IV antibiotic use, i.e. a rise in serum creatinine in a patient receiving IV Vancomycin; blood dyscarias in a patient receiving beta lactam therapy

Decrease Decrease 30 day readmission rates for patients managed by ID service at PUH/MUH/MWH from 32% to 18%

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Current Participating HospitalsPATIENTS IDENTIFIED VIA CONSULTATION

› UPMC Montefiore (MUH)

› UPMC Presbyterian (PUH)– Transplant and non-transplant

patients

› Magee Women’s Hospital of UPMC (MWH)

› UPMC Shadyside/Hillman– Transplant patients w/blood cancers

PATIENTS IDENTIFIED VIA TELECONSULT

› UPMC Jameson

› UPMC Northwest

› UPMC Horizon– Shenango Valley– Greenville

Current Staffing› Medical Director› 9 MDs to staff 6 half day clinics per week › 2 APPs to staff 6 half day clinics per week› 1 Pharmacist› 1 Coordinator› 2 Nurses› Patients are evaluated inpatient by UPP Infectious Disease service

and referred to program› Visits can occur at Falk, Telemed Clinics (Northwest, Bedford,

Jameson) or through MyUPMC Telemedicine app

Continued Growth

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UPMC All UPMC Unique Patient All Unique Patients

2019 data through June 2019

Protocol for monitoring› IV Antibiotic discharge note› Outpatient evaluation within 7 days of discharge and prior to

end of therapy› Weekly lab monitoring based on IDSA recommendations› Epic flowsheet for lab monitoring› Collaborative practice agreement› Weekly huddle› Partner with Home health agency & Infusion pharmacy

What’s included in the Antibiotic Discharge Note› Patient name, MRN, discharge floor, Demographics, Height, Weight› Type of Infection› Monitoring MD › Office phone & fax number› Antibiotic name, dose, frequency, route. Antibiotic end date

– IDSA recommended lab auto-populates based on chosen antibiotic

› Follow up testing needed, ie CT scan, MRI, echo, blood cultures› When to follow up in clinic› Routine picc care orders: flushes, tubing etc› Antibiotic line lock orders› Additional fluid orders› Note incorporates into the Clinical Discharge summary

EPIC Documentation› Home IV Therapy episode

– Creates a flowsheet for lab tracking to identify lab trends more timely– Can be routed amongst team members for communication

› OPAT Patients are also tracked on a calendar that can be sorted by end date of antibiotic to aid with huddle review

General Characteristics

Readmission Rates– Overall Readmission rate 18.5% for those with ID Clinic follow-

up; 53.6% readmission rate for those with no follow-up

UPMC HealthPlan Video Visit Pilot› HealthPlan patients discharged from PUH/MUH can be offered

a video visit in place of in-office follow up› Have to have MyUPMC and ideally a smartphone

› Transplant patients excluded› Patients with a heart or lung infection also excluded› Uses vidyo platform through EPIC› Pilot started in mid-July 2019

› Data to come

Alternatives to OPAT

› Conducted at a French 830 bed acute care teaching hospital, average of 30,000 admissions per year

› Observational, retrospective› Patients were managed by ID based on European guidelines and

had to have definitive or possible IE by Duke’s criteria› Protocol for switch from IV to PO› Minimum duration of 7 days of IV prior› Evaluated daily: patient condition, fever resolution, CRP reduction,

negative blood cultures, normal WBC count, normal creat, normalization of imaging

› ALL criteria fulfilled to switch to PO

Patient Demographics

Outcomes› Patients in the PO group had

fewer comorbidities and criteria of severity

› Less likely to be Staph Aureus› Median time to switch was 21

days (0-70)– For Oral streptococci 14 days (7-

42)– Staph aureus 28 days (1-56)– Enterococci 28 days (14-42)– Other 21 days (0-70)

› Median range of follow-up was 5 months (0-147)

› 92 patients died (22%); 11 (3%) had relapse and 12 (3%) had reinfection

› Death occurred in 76 (36%) in IV arm vs 16 (8%) in PO arm

› then adjusted for age > 65, type I diabetes, immunosuppression, removal of PV, and S.aureus -> no increased risk of mortality in the PO group

› Relapse rate: 2 in PO vs 9 in IV› Reinfection rate 4 in PO vs 8 in IV

Oral regimens

› Investigator-initiated, multicenter, randomized, unblinded, noninferiority trial completed at cardiac centers in Denmark

› Adults, 18 or older in stable condition with left sided endocarditis– Native or prosthetic valve, left sided endocarditis

› Primary outcome: all-cause mortality, unplanned cardiac surgery, clinically evident embolic events or relapse of bacteremia with primary pathogen from randomization through six months after antibiotic completed

› July 2011 to August 2017

Patient Demographics

Outcomes

Oral group shifted from IV at a median of 17 daysOral group included 2 different antibiotics from 2 different classes that were both bactericidal

Rates of primary outcome in prespecified groups

Conclusion of the POET Trial & Limitations› In clinically stable patients with left sided endocarditis with

E.faecalis, Streptococcus, CONS or MSSA that have completed nearly half of the IV course for endocarditis may transition to PO regimen consisting of 2 levels

› Only 20% of screened population was randomized› No MRSA› Not clear if this will work in IVDA

› More trials needed

› Enrolled patients with bone or joint infections at 26 UK centers› IV therapy continued for 7 days from surgery date or 7 days total

before transition to PO› Patients randomly assigned to complete six weeks of IV vs PO but

could be followed by ongoing oral antibiotics› Primary end-point was treatment failure one year after

randomization› Median duration of antibiotics was 78 days in the IV course & 71 in

the PO course – IV arm was mainly glycopeptides & cephalosporins whereas PO was

quinolones or combination therapy– Rifampin could be added at any point but patients in the PO arm tended to

receive more rifampin then the IV arm (*though outcomes did not vary)

Baseline Characteristics

Outcomes› More catheter associated complications in the IV course› No difference in incidence of C. difficile› Hospital LOS was 14 days in the IV arm vs 11 in the PO arm

Conclusion› Oral therapy was non-inferior to IV therapy for orthopedic

infections › Half of the patients either did not have evidence of deep

infection or data was missing› Heterogeneous population› Majority had surgery in addition to antibiotic course

Oral therapy Conclusions› May be a viable option in select circumstances› More trials need to be conducted to address PWID population

Conclusions

› OPAT is a well established model of care since the 1970s in the US

but has increased in popularity in the last decade

› OPAT can be used to treat all types of infections

› OPAT is safe & efficacious with various antibiotic classes

› UPMC OPAT program has been in existence since December 2013

› Successful reduction in 30 day readmission rates, especially notable in patients that follow up in ID clinic

› Various options for ID follow

› Oral options may be considered in select scenarios but more trials

still needed