APPLYING THE CORE ELEMENTS OF ANTIMICROBIAL STEWARDSHIP TO

CLINCAL PRACTICE

Cynthia A Mayer, DO, FACOI Infectious Disease Associates of Tampa Bay

September 2019

FOMA

Financial disclosures

• I have no financial disclosures

Objectives

• Discuss untoward effects of antibiotic use

• Review the rationale for an Antimicrobial Stewardship Program

• Define the Core Elements of an Antimicrobial Stewardship Program

• Describe drug, dosing and duration for selected infections

Antibiotics

• Transformed medicine

• Treatment for lethal infections and making other medical advances possible, chemo, transplant

• Reduce morbidity and mortality

Untoward Effects

• 20-50% of all antibiotics prescribed are unnecessary or inappropriate*

• Adverse reactions, allergies, drug-drug interactions, C diff, abx associated diarrhea

• Increased health-care cost

• Antibiotic-resistant infections

* CDC

Sinus Infections

• 70% of antibiotic courses for sinuses infections were longer than recommended

• Most courses were 10 days or longer

• IDSA guidelines recommend 5-7 days of antibiotics, if needed for uncomplicated sinus infections

“Antibiotic Therapy Duration in U.S. Adults With Sinusitis,” The Journal of the American Medical Association: Internal Medicine,” July 2018

Adult Hospitalized with Community Acquired Pneumonia

• Antibiotic therapy was too long -10 days- for 70% of adult patients hospitalized for CAP

• IDSA and ATS published guidelines in 2007

recommending a minimum of 5 days with 7 or more days rarely necessary

“Duration of Antibiotic Use Among Adults With Uncomplicated Community-Acquired Pneumonia Requiring Hospitalization in the United States,” Clinical Infectious Disease, April 2018

Fluoroquinolones • Fluoroquinolones are unnecessarily prescribed for UTIs

and Respiratory conditions • 20% of fluoroquinolone prescriptions were not the

recommended first-line treatment • Serious reactions include tendon rupture, peripheral

neuropathy, exacerbate muscle weakness in myasthenia gravis, C diff infection

• 2016 FDA issued a warning advising use only for conditions for which no alternative treatment option was available

• 2018 FDA warned of increased risk of ruptures or tears in the aorta

“Opportunities to Improve Fluoroquinolone Prescribing in the United States for Adult Ambulatory Care Visits, “ Clinical Infectious Diseases ,January 2018

Antibiotic Resistance

• Increase in antibiotic resistance esp. MRSA, VRE, CRE, ESBL

• Can even impact health of patients who are not even exposed

• 2M are infected with antibiotic-resistant organisms

• Resulting in ~ 23,000 deaths annually

• CDC: an important safety and public health issue

http://www.cdc.gov/media/dpk/2013/dpk-untreatable.html. Accessed December 27, 2017.

Antibiotic Development: Dry Pipeline

Antibiotic Stewardship

• 2014: CDC recommended that all acute care hospitals implement antibiotic stewardship programs

• March 2015: National Action Plan for Combating Antibiotic-Resistant Bacteria issued by the White House which calls for establishment of ASPs in all acute care hospitals by 2020 – and for CMS to issue a Condition of Participation that

hospitals develop a program – based on recommendations from the CDC Core Elements

of Hospital ASPs

• January 1, 2017: The Joint Commission new Medication Management standard for hospitals and nursing care centers, MM.09.01.01 addressing antimicrobial stewardship, became effective

Antibiotic Stewardship

What is it?

• Definition: A system of informatics, data collection,

personnel, and policy/procedures which promotes the optimal selection, dosing, and duration of therapy for antimicrobial agents throughout the course of their use

• Purpose:

– Limit inappropriate and excessive antibiotic use

– Improve and optimize therapy and clinical outcomes for the individual infected patient

Ohl CA. Seminar Infect Control 2001;1:210-21. Ohl CA, Luther VP. J. Hosp. Med. 2011;6:S4 Dellit TH, et. al. Clin Infect Dis. 2007;44:159-177

• Is pertinent to inpatient, outpatient, and long-term care settings

• Is practiced at the

– Level of the patient

– Level of a health-care facility or system, or network

• Should be a core function of the medical staff

(i.e. doctors and other healthcare providers)

• Utilizes the expertise and experience of clinical pharmacists, microbiologists, infection control practitioners and information technologists

Antibiotic Stewardship

Where does it apply?

Goals of ASPs

• Antibiotic Stewardship Programs (ASPs) can optimize treatment of infections and reduce adverse events

• Improve quality of patient care

• Improve patient safety

• Increase infection cure rates

• Reduce treatment failure

• Increase frequency of correct prescribing for therapy and prophylaxis

• Reduce rates of CDI and antibiotic resistance

• Often while saving money

Core Elements of Hospital Antibiotic Stewardship Programs

• Leadership Commitment: Dedicating necessary human, financial and information technology resources

• Accountability: Appointing a single leader responsible for program outcomes. Experience with successful programs show that a physician leader is effective

• Drug Expertise: Appointing a single pharmacist leader responsible for working to improve antibiotic use.

• Action: Implementing at least one recommended action, such as systemic evaluation of ongoing treatment need after a set period of initial treatment (i.e. “antibiotic time out” after 48 hours)

• Tracking: Monitoring antibiotic prescribing and resistance patterns • Reporting: Regular reporting information on antibiotic use and

resistance to doctors, nurses and relevant staff • Education: Educating clinicians about resistance and optimal

prescribing

Action examples

• Policies that support optimal antibiotic use – Documentation dose, duration and indication – Develop and implement facility specific treatment recommendations

• Interventions to improve antibiotic use – Antibiotic “Time outs”

• Reassess need and choice when clinical picture is clearer and more diagnostic information is available, 48 hours after initiation – Does patient have an infection – Right antibiotic, dose and route – Targeted antibiotics, de-escalate – Define duration of antibiotics

– 6 D’s: Diagnosis, Drug, Dose, Duration, De-escalation, Documentation

Action examples

• Interventions to improve antibiotic use, cont. – Prior authorizations – restricted use of some antibiotics based on

spectrum, cost, toxicities

– Prospective audit and feedback

• Review by ASP team of broad spectrum or multiple antibiotic use

– Pharmacy-driven interventions

• Automatic changes from IV to po

• Dose adjustments in cases of organ dysfunction

• Dose optimization, therapeutic drug monitoring

• Automatic alerts: duplication

• Time-sensitive automatic stop orders

• Detection and prevention of antibiotic-related drug-drug interactions

Action examples

• Interventions to improve antibiotic use, cont.

– Infection and syndrome specific interventions

• Community-acquired pneumonia - focus on diagnostic accuracy, tailoring of therapy, optimize duration

• Urinary tract infections – help avoid unnecessary urine cultures and treatment of patients with asymptomatic bacteriuria

• Skin and soft tissue infections - avoid overly broad spectrum and ensure correct duration of treatment

Some Non-Infectious Causes of Fever

• Medications

• Autoimmune

• Endocrine

• “Central fever”

• Neoplasms

• Hematomas, clots, PE’s

• Few miscellaneous causes (FMF, gout, etc.)

Some Non-Infectious Etiologies of Leukocytosis

• Medication (glucocorticosteroids, lithium, etc.)

• S/P splenectomy

• Tissue necrosis

• Myeloproliferative disorders

• Acute GI bleed

• Any acute physical stressor (post-op, burns, etc.)

Appropriate Antibiotic Duration for Selected Infections in Adults

Infection Antibiotic, Duration

UTI

Acute uncomplicated cystitis, women

TMP-SMX, 3 d Nitrofurantoin, 5 d Fosfomycin 3 g for 1 dose Beta-lactams, 3-7 d

Acute uncomplicated pyelonephritis, women

Fluoroquinolones (levofloxacin, 5 d, ciprofloxacin, 7d) TMP-SMX, 14 d Beta-lactam, 10-14 d

Complicated, including pyelonephritis Fluoroquinolones, 7d for hospitalized patients, 10-14 d for patients with bacteremia/urogenital abnormalities

Appropriate Antibiotic Duration for Selected Infections in Adults

Infection Antibiotic, Duration

Pneumonia

Community acquired At least 5 d, with 48-72 h afebrile and <1 clinical instability sign (e.g., elevated HR or RR, decreased SBP, arterial oxygen saturation) before discontinuation of therapy A longer duration may be necessary in some patients (e.g., previous abx treatment, immunosuppressed, requiring chest tube placement, mechanical ventilation, severe sepsis)

Nosocomial 7 d for both HAP and VAP

Acute exacerbation of COPD and chronic bronchitis

Courses of <5 d is as effective as >7 d for mild to moderate cases

Acute bacterial sinusitis 5 d course had effectiveness comparable to 10 d course. Amoxicillin, amoxicillin/clavulanate, Doxy, respiratory quinolones

Appropriate Antibiotic Duration for Selected Infections in Adults

Intraabdominal 4-7 d course if infection source controlled; otherwise, a longer course may be necessary

Cellulitis Course of 5 d is as effective as 10 d; longer durations may be necessary if infection has not improved within 5 d

Bacteremia 10-14 d with removal focus and no endocarditis For uncomplicated Enterobacteriaceae of GI or GU origin, can finish with an oral antibiotic with good bioavailability (e.g., quinolones, TMP-SMX)

Syndromes with Potential for Antibiotic Overuse

• Catheter Associated UTI

• Asymptomatic Bacteriuria

• Abnormal CXR or CT scans

• Viral Infections

• Colonization

• Other

Catheter Associated UTI

• Signs / symptoms c/w UTI and no other source – Fever, chills, dysuria, AMS, flank or suprapubic pain, etc.

• >103 of colony forming units of pathogen • From patient with catheter removed / changed within

48 hrs.

• In a catheterized patient, pyuria is not diagnostic of CA-UTI or CA-asymptomatic bacteriuria. However, the absence of pyuria does suggest a diagnosis other than CA-UTI.

• Only treat asymptomatic bacteriuria in pregnant females or those to undergo urologic procedures.

Horton TM, et al. CID 2010; 50:625-663

Treatment of Asymptomatic Bacteriuria in the Elderly

Multiple prospective randomized clinical trials have shown no benefit

• No improvement in “mental status”

• No difference in the number of symptomatic UTIs

• No improvement in chronic urinary incontinence

• No improvement in survival

Prevalence of Asymptomatic Bacteriuria

Age (years) Women Men

20 1% 1%

70 20% 15%

>70 + long-term care 50% 40%

Spinal cord injury 50% 50% (with intermittent catheterization)

Chronic urinary catheter 100% 100%

Ileal loop conduit 100% 100%

Nicolle LE. Int J Antimicrob Agents. 2006 Aug;28 Suppl 1:S42-8.

Summary of Asymptomatic Bacteriuria Treatment

• Treat symptomatic patients with pyuria and bacteriuria • Don’t treat asymptomatic patients with pyuria and/or

bacteriuria • Define the symptomatic infection anatomically • Dysuria and frequency without fever equals cystitis • Dysuria and frequency with fever, flank pain, and/or

nausea and vomiting equals pyelonephritis • Remember prostatitis in the male with cystitis symptoms • Only treat asymptomatic bacteriuria in pregnant females

or those to undergo urologic procedures

• CAP: often a difficult diagnosis

• X-rays can be difficult to interpret. Infiltrates may be due to non-infectious causes.

• Examples:

–Atelectasis

–Malignancy

–Hemorrhage

–Pulmonary edema

Do not Treat Sterile Inflammation or Abnormal Imaging Without Infection

Example: community-acquired pneumonia (CAP)

• Pneumonia is not present in up to 30% of patients treated

• Do not treat abnormal x-rays with antibiotics if the patient does not have systemic evidence of inflammation (fever, wbc, sputum production, etc.)

• Discontinue antibiotics initially started for pneumonia if alternative diagnosis revealed

Community-Acquired Pneumonia (CAP)

• Acute bronchitis

• Common colds

• Sinusitis with symptoms less than 7 days

• Pharyngitis not due to Group A Streptococcus spp.

Gonzales R, et al. Annals of Intern Med 2001;134:479 Gonzales R, et al. Annals of Intern Med 2001;134:400 Gonzales R, et al. Annals of Intern Med 2001;134:521

Do not Treat Viral Infections with Antibiotics

Treat Bacterial Infection, not Colonization

• Many patients become colonized with potentially pathogenic bacteria but are not infected

– Asymptomatic bacteriuria or Foley catheter colonization

– Tracheostomy colonization in chronic respiratory failure

– Chronic wounds and decubiti

– Lower extremity stasis ulcers

– Chronic bronchitis

• Can be difficult to differentiate

– Presence of WBCs not always indicative of infection

– Fever may be due to another reason, not the positive culture

• Limit duration of surgical prophylaxis to <24 hours perioperatively

• Use rapid diagnostics if available

(e.g. respiratory viral PCR)

• Solicit expert opinion if needed

• Prevent infection

– Use good hand hygiene and infection control practices

– Remove catheters

Other Tenets of Antibiotic Stewardship

Other Tenets of Antibiotic Stewardship

• Re-evaluate, de-escalate or stop therapy at 48-72 hours based on diagnosis and microbiologic results

• Re-evaluate, de-escalate or stop therapy with transitions of care (e.g. ICU to step-down or ward)

• Do not give antibiotic with overlapping activity

• Do not “double-cover” gram-negative rods (i.e. Pseudomonas sp.) with 2 drugs with overlapping activity

• No need to add Flagyl to B-lactam/B-lactamase inhibitor drugs or carbapenems for anaerobic coverage

Summary