Pisano.SCACM talk.pptx [Read-Only]...9/17/2018 1 Antimicrobial Stewardship and the Microbiology Lab: Opportunities for Collaboration in Optimizing Choice of Antibiotic Therapy when

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Antimicrobial Stewardship and the Microbiology Lab: Opportunities for Collaboration in Optimizing Choice of

Antibiotic Therapy when Treating InfectionsJennifer Pisano, MD

Medical Director, Antimicrobial Stewardship ProgramUniversity of Chicago Medicine

Objectives

• Explain the importance of microbiology lab and antimicrobial stewardship program collaboration

• Identify key timepoints in patient care when the microbiology lab and stewardship team can focus interventions

• Describe opportunities for both systems‐based and behavioral interventions to guide prescribing

THE COMMUNITY

HOSPITALS

AGRICULTURE/AQUACULTURE

THE ENVIRONMENT

Development and Spread of Antibiotic

Resistance

Adapted from: Francesca Prestinaci, Patrizio Pezzotti& Annalisa Pantosti (2015)Antimicrobial resistance: a global multifaceted phenomenon, Pathogens and Global Health, 109:7, 309-318, DOI: 10.1179/2047773215Y.0000000030

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Why is resistance important?

Making drugs for diseases that can be cured is not as profitable as drugs for chronic diseases

Overuse of antibiotics• Antimicrobial Resistance• Collateral damage

• Microbiome disruption • Antibiotic toxicities• Clostridium difficile

55% of patients received at least 1 dose of antibiotics during their hospital visit

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What is Antimicrobial Stewardship?Coordinated strategies implemented by a multidisciplinary team to optimize

the use of antimicrobials

Patient outcomes

Toxicity, Clostridium difficile, Antibiotic resistance

What is Antimicrobial Stewardship?

Gerding DN. The search for good antimicrobial stewardship. Qual Improv. 2001;27(8):403-404.Joseph J. The role of carbapenems in the treatment of severe nocsocomial respiratory tract

infections. Expert Opin Pharmacother. 2008:9(4):561-575.

Antibiotic effects on the microbiome

Jernberg C et al. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiollogy (2010), 156, 3216-3223

Effects of antibiotic therapy on the microbiome are long-lasting and support the colonization and spread of resistant bacteria

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Culture of Empiricism

• Pathogen‐specificdrugs

• Manipulating the immune response

• Further development of rapid diagnostics

• Antimicrobial Stewardshipo Optimize use of current therapieso Shorten antibiotic courses

• Identify combinations that reduce emergence of resistance

• Culture‐>rapid diagnostics

How can we make it easier to do the right thing?

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Making decisions regarding antimicrobial therapy is hard.

Clinical exam

Labs

Imaging

Culture results

Patient History

Molecular Diagnostics

Biomarkers

Collaboration is key

Nurses

Patients

Pharmacists

Physicians

Clinicians

Information technologists

Nursing assistants

Microbiologists

Laboratory technologists

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Diagnostic stewardshipJust because you can, doesn’t mean you should…

• Earlier, more targeted therapies• Decrease the use of empiric

antibiotics and collateral damageo Clostridium difficileo Toxicitieso Development of resistanceo Affects on the microbiome

Messacar K et al. Implementation of Rapid Molecular Infectious Disease Diagnostics: the role of diagnostic and antimicrobial stewardship. J ClinMicrobiol 55:715‐723. https://doi.org/10.1128/JCM.02264‐16.

DiagnosticsAntimicrobials

Stewardship

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Timepoints to consider interventions

Evaluating the patient

Ordering diagnostics

Collecting specimens

Performing diagnostic testing

Reporting results

Interpreting Results

Antibiotic choice‐

Treatment PlanFollowing up


• Relies on provider to assess pretest probability of diagnosis to guide testingEvaluating the patient

• Education, clinical pathways/EMR decision support, prior authorization, indication‐based ordering; decreasing treatment of FALSE POSITIVE testsOrdering diagnostics

• Timely ordering by provider, collection by staff in appropriate container and timing of transport to lab for processingCollecting specimens

• Transparent in processes, reflex testing, rapid diagnostics, TATPerforming diagnostic testing

• Timely, with guidance embedded in reports or direct communication to impact prescribingReporting results

• ASP direct communication, added comments or links to guidelinesInterpreting Results

• ASP recommendations and post‐prescription review, dose, duration, combination therapyAntibiotic choice‐Treatment Plan

• Post‐prescriptive review, feedbackFollowing up

Antibiotic Stewardship = optimization of therapy. This can also mean broader, more costly or more toxic coverage.

Morgan DJ et al. Diagnostic Stewardship—Leveraging the Laboratory to Improve Antimicrobial Use. 2017;318(7):607-608. doi:10.1001/jama.2017.8531

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Reporting results


Antibiotic choice‐

Treatment PlanFollowing up

MICROBIOLOGY LAB/ANTIMICROBIAL STEWARDSHIP COLLABORATION IS KEY






Reporting results


Modify antimicrobial chemotherapy

Following up

MICROBIOLOGY LAB/ANTIMICROBIAL STEWARDSHIP COLLABORATION IS KEY

Will the clinician understand the test result?

Will the clinician act on the test result promptly to modify the

treatment plan?

Will the clinician know the result is available?

Did the intervention have the

intended effect? PPR/Feedback?

Approaches to affect prescribing

• Selective reportingoHiding resultso Suppression based on intrinsic resistanceoGrouping species into more familiar nomenclature

• Cascade reporting• Embedding educational/interpretive comments

o Links to guidelines, pathways, antibiograms• Antimicrobial stewardship as the messenger • Post‐prescriptive review and feedback

Often requires a combination of approaches

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Selective reporting

Pulcini et al. Selective reporting of antibiotic susceptibility test results in European countries‐an ESCMID cross‐sectional survey. Int J of Antimicrobial Agents 49 (2017) 162‐166

Selective reporting based on resistance mechanism ‐ AmpC beta‐lactamases

“Cefepime is usually effective therapy for infections caused by this pathogen”

Cascade reporting• Algorithm‐based susceptibility reporting • Provides limited groups of susceptibility results based on

o Epidemiologic data o Formulary availability o Toxicityo Spectrum of activity and risk of development of resistanceo Cost

• Secondary antibiotic therapy (more broad‐spectrum, costly, toxic, higher impact of resistance) is only reported if an organism is resistant to the first cascade

• Susceptibilities are reported from at least 2 classes of antibiotics for cases of allergy

Morency‐Potvin et al. Antimicrobial Stewardship: how the microbiology laboratory can right the ship. Clinical Microbiology Reviews Vol 30 issue 1, Jan 2017. https://www.publichealthontario.ca/en/BrowseByTopic/InfectiousDiseases/AntimicrobialStewardshipProgram/Documents/ASP_Strategy_Cascading_Microbiology_Reporting.pdf

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Cascade reportingAdvantages

• Decreases use of more toxic, unnecessarily broad‐spectrum therapy

o Encourages use of narrow‐spectrum, cost‐effective therapy

• Potential to improve susceptibility to suppressed agents

• If system can be automated, will require minimal intervention

Disadvantages• Reporting algorithms may become complicated

o Investment in creation, oBuy in from key stakeholders

• Depends on provider’s interpretation of the reports

oMay assume not reported agents are resistant and prescribe redundant therapy

Morency‐Potvin et al. Antimicrobial Stewardship: how the microbiology laboratory can right the ship. Clinical Microbiology Reviews Vol 30 issue 1, Jan 2017. https://www.publichealthontario.ca/en/BrowseByTopic/InfectiousDiseases/AntimicrobialStewardshipProgram/Documents/ASP_Strategy_Cascading_Microbiology_Reporting.pdf

Johnson LS et al. Impact of microbiology cascade reporting on antibiotic de‐escalation in cefazolin‐susceptibile gram‐negative bacteremia. Eur J Clin Microbiol Infect Dis (2016) 35:1151‐1157.

• 6 month pre/post study at 2 teaching hospitals in Atlanta

• E. coli was most common organism in each group

• Most common source of bacteremia was the urinary tract

• Rate of de‐escalation was higher in the post CR period (71% vs. 48%, p=0.043)

• Decrease in anti‐pseudomonal beta‐lactam use, increase in ceftriaxone therapy

• No differences in safety outcomes, LOS

Cascade reporting

Intervention:Ciprofloxacin susceptibility to

Enterobacteriaceae was suppressed when there was a lack of resistance to the antibiotics

on the gram‐negative panel

• Ciprofloxacin utilization decreased from 87 (95% CI, 83.7 to 91.2) to 39 (95% CI, 35.0 to 44.0) DDD per 1000 patient days post intervention and maintained up to 24m post.

• Increase use of amoxicillin‐clavulanate • E. Coli S to ciprofloxacin was higher than expected post intervention p

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Use of comments in microbiology reports to guide therapy• Clear and concise messaging added to result reporting to guide therapy

• May include links to clinical pathways/decision support• Automated messages preferred

oManually entered comments may be forgotten• CLSI recommends few therapy‐related comments

“commensal respiratory flora only: No S. aureus/MRSA or P. aeruginosa”

“commensal respiratory flora” • 210 patients• De‐escalation/discontinuation more likely in intervention group (39%

vs. 73%, p

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CLSI‐recommended comments

Comments regarding: • inferred susceptibility, • choice of antimicrobial,

• dose depending on diagnosis combination therapy

Adapted from: Morency‐Potvin P et al. Antimicrobial Stewardship: how the microbiology lab can right the ship. 2017. Clin Microbiol Rev 30:381‐407.

Other Therapy‐related comments

Diagnosis Issues Positive urine cultures should prompt targeted antimicrobial therapy only if the patient 1. has symptoms of cystitis or pyelonephritis, 2. is pregnant, or 3. will soon undergo and invasive urologic procedure; apart from these clinical indications, patients with asymptomatic bacteriuria do not benefit from antibiotic therapy

Duration of therapy S. aureus bacteremia usually requires a minimum of 14 days of therapy; longer therapy is often needed to treat or prevent complicated infections; expert consultation is advised.

Reference to documentation Refer to local guidelines for treatment recommendations of respiratory tract infections (ADD A HYPERLINK!)

Suggestions for alternatives In our institution, clindamycin is the preferred agent used to treat this pathogen in patients with IgE‐medicated allergy to penicillin

Selective or cascade susceptibility reporting

Only first‐line recommended antimicrobials appear in this report; contact the laboratory for additional susceptibility testing if alternate agents are needed, e.g., due to allergy

Reference to antimicrobial stewardship program services

Contact the antimicrobial stewardship team to choose the best agent to treat this infection (e.g., for unusual or MDRO pathogens)

Indicate preferred agents Bold or highlight preferred agents based on cost, epidemiologic data

Adapted from: Morency‐Potvin P et al. Antimicrobial Stewardship: how the microbiology lab can right the ship. 2017. Clin Microbiol Rev 30:381‐407.

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Comments and selective reporting based on resistance mechanism identified ‐ CRE

Instructions for ID consultation embedded in the comment

Reflexive change in SIR reporting based on resistance mechanism

Comments and selective reporting based on resistance mechanism ‐ ESBLs

Cefepime and ceftriaxone are reported as resistant even though MIC is in S‐SDD range

Timbrook TT et al. Current and future opportunities for rapid diagnostics in antimicrobial stewardship. Med Clin N Am 102 (2018) 899–911

Rapid diagnostics

Very sensitiveTimely

May pick up false positive results

Difficult to interpret when multiple positives

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Rapid diagnostics without ASP intervention does not affect time to optimal antibiotic prescribing

Goff DA et al. Using Rapid diagnostic tests to optimize antimicrobial selection in antimicrobial stewardship programs. Pharmacotherapy 2012;32(8):677‐687; Frye et al, Clinical impact of a rel‐time PCR assay for rapid identification of staphylococcal bacteremia. J Clin Micro , 2012 Jan;50(1):127‐33. Cosgrove et al Use of PNA FISH for blood cultures growing gram‐positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy. Diagn Microbiol Infect Dis 2016;86(1):86‐92. Buehler SS, Madison B, Snyder SR, Derzon JH, Cornish NE, Saubolle MA, Weissfeld AS, Weinstein MP, Liebow EB, Wolk DM. 2016. Effectiveness of practices to increase timeliness of providing targeted therapy for inpatients with bloodstream infections: a laboratory medicine best practices systematic reviewand meta‐analysis. Clin Microbiol Rev 29:59–103. doi:10.1128/CMR.00053‐14.

• 2012: Frye et al, reported that with the use of rtPCR to differentiate Staph spp. and MSSA/MRSA

o Time to identification was significantly reduced (10.5 v 15.9h, p

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RDT + ASP Review

• Cairns et al, 2016oPatients were more likely to be on active and appropriate antimicrobial therapy at 72h when stewardship review was performed in addition to testing with MALDI‐TOF in patients with positive blood cultures.

• Nagle et al, 2014oMALDI‐TOF + AST review in CoNS bacteremiaoReal‐time ASP pages 6a‐11:30p and 24h emailsoBacteremic patients started on optimal therapy sooner in the AST group (58.7 vs 34.4 h, p=0.030) and had decreased mortality (21.7% v 3.1%, p=0.023)

oDecreased duration of unnecessary therapy (1.31 v 3.89 days, p=0.032)oDecreased vancomycin assays 2 v 0.9 (p

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Multiplex PCRs from non‐sterile sites

Do I treat them all?!?!

GI mPCR panel: Does finding more bugs lead to inappropriate drugs?• 760 of 3066 GI mPCR tests performed were positive (25%).

• 108 (14%) of positive test results identified multiple pathogens (2 to 5)

• Immunocompetent adults with a positive GI mPCR were significantly more likely to receive antibiotics compared to all hospitalized patients (75% vs. 40%, p

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GI mPCR possible commentsOrganism CommentCampylobacter Illness generally mild and self‐limited. Consider treatment for severe infections and in elderly,

pregnant or immunocompromised hosts.C. difficile toxin A/B Up to 15% of people are asymptomatic carriers of Clostridium difficile. For guidance in

treatment of infections due to C. diff, please refer to clinical pathway on the ASP websiteSalmonella Prolonged periods of asymptomatic shedding have occurred after infection with Salmonella

species Enteroaggregative E. coli (EAEC)Enteropathogenic E. coli (EPEC)

Enteropathogenic E. coli (EPEC) and Enteroaggragative E. coli (EAEC) have been detected in stools of both asymptomatic and symptomatic patients. Infection with only certain strains leads to symptomatic diarrheal illness .

Norovirus GI/GII Asymptomatic shedding of virus has been reported, prolonged periods of shedding have been seen post‐infection in immunocompromised hosts

Benefit from post‐result review?

Respiratory mPCR

• Clinicians will act on influenza negative results and stop oseltamivir stopped if influenza negative

• Empiric antibiotic therapy was discontinued in only 25% of patients with a positive result indicating viral infection

o 70% of patient + for influenza treated with antibiotics

Yee et al. AJIC Nov 2016. http://doi.org/10.1016/j.ajic.2016.04.221

Adenovirus Coronavirus HKU1/NL63/229E/OC43

Human Rhinovirus/enterovirus

Parainfluenza 1/2/3/4

RSV Human Metapneumovirus

Influenza A Influenza B Bordetella pertussis

Chlamydophila pneumoniae

Mycoplasma pneumonia

Respiratory mPCREmbedding

epidemiologic data may make providers more comfortable stopping antibiotics if the Respiratory

mPCR result correlates with “What’s going

around”

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Respiratory mPCR possible comments

Organism CommentInfluenza Patients may benefit from oseltamivir treatment in the first 48h of symptom onset.

For treatment recommendations for immunocompomised hosts, consider discussing with ID provider.

General With positive respiratory viral panel result, consider discontinuing empiric antibacterial therapy as unnecessary antibiotic therapy may lead to untintended consequences including C. diff, development of resistant bacteria and antibiotic toxicities.

Following‐up

• Talk to your primary prescribers• Consider surveys or focus groups after modifications are made• Actively seek out feedback regarding the accuracy, timeliness, impact and acceptability of the change

• Identify super‐users/key stakeholders to providing education and offer support in their specific clinical area

Summary

• Collaboration between the microbiology lab and antimicrobial stewardship program is necessary to identify opportunities to affect antibiotic prescribing

• Reporting results, interpreting results, modifying antimicrobial chemotherapy are 3 important time points to optimize antimicrobial prescribing.

• Interventions may be systems based (i.e., algorithms to guide selective reporting) or behavioral based (i.e., nudges in the form of comments in reports)

• ASP‐provider communication is paramount in building trust, offering education and ensuring appropriate modifications in therapy are performed

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