Antimicrobial Stewardship (PROA) Journal Watch

Antimicrobial Stewardship(PROA)

Journal Watch

(Nov´14-Feb´15)

José Ramón Paño Unidad de Enfermedades Infecciosas y Microbiología Clínica

Hospital Universitario La Paz (Madrid)February 11th,2015

Methods

Surveillance (RSS feeds)• CID, JID, JAC, AAC, The Lancet Infectious Diseases,

JAMA, NEJM• Twitter

Period: Nov 2014-Feb 2015

Selection• I have followed my own criteria • Of initially selected articles, some will be

commented

All references are linked to PubMed

http://www.pubmed.org

Outline

• Determinants of antimicrobial use

• Monitoring/quality of antimicrobial use

• Interventions to improve antimicrobial use

• Thinking out of the box (antimicrobial stewardship)

Determinants of antimicrobial use

Linder JA. JAMA Intern Med. 2014 Dec;174(12):2029–31.

• Decision fatigue: erosion of self-control after making repeated decisions

Easy choice(frequently inappropriate)

Judges: Prolonged sessions% Parole

Doctors &: At the end of the day ABX in URI?

http://www.ncbi.nlm.nih.gov/pubmed/?term=25286067


Setting

• 23 primary care practices (USA) -204 physicians-

• Acute respiratory infections (ARI) in adults (18-64)

• May 2011-September 2012

Methods• Billing and electronic health records were merged

• ARI were classified diagnoses as “antibiotics sometimesindicated” or “antibiotics never indicated”

• ARI visits by which occurred during two 4-hour sessions—8 AM to noon and 1 PM to 5 PM

• Using logistic regression, the probability of antibiotic prescribing as a function of session hour, N of visits per session, calendar month of visit, patient- level confounders was estimated



• Otitis• Pneumonia• Strep

Pahryngitis

• URI• Influenza• Non-Strep

Pharyingitis

21 867 ARI visits



Remedies for decision fatigue might include time-dependent decision support, modified schedules, shorter sessions, mandatory breaks, or snacks

Any hospital-based antibiotic prescribing-related decision fatigue circumstance?


Monitoring/Quality of antimicrobial use

Objectives:

• The frequency with which patients were started on empirical ABX

• characteristics of the empirical regimen

• clinical characteristics of patients at the time of starting antimicrobials

• patterns of changes to empirical therapy at different timepoints

• and modifiable factors associated w/ changes to the empirical regimen (day 5)

To assess:

Methods

• Multicenter chart-review 2009-10 by ID physicians: 6 centers/4 days for each center/50 records/center-day (randomly selected)

• Only adult patients in non-psychiatric wards were included

• Variables: demographics, outpatient antimicrobial use and allergies, and the name, indication, start and stop dates, and documentation source, with a standardised electronic form.

• When documentation was conflicting, reviewers were asked to make a clinical judgment based on all the information available in the record

• Microbiology and radiology studies were deemed relevant to this analysis if they were collected on or before the day antibiotic therapy was started

• Review of therapy adjustments: The analysis was focused on patterns and factors associated with the decision to modify antimicrobial therapy in the first 5 days of treatment (Kollefcriteria)

Braykov NP. Lancet Infect Dis. 2014 Dec;14(12):1220–7.


Results• 6812 patients were admitted to hospital on the four review dates, of

whom 4119 (60%) had an active antimicrobial order (46.6-78.8)


• 67% pacientes sin fiebre

• 33% sin fiebre ni leucocitosis

• Cultures obtained before ABX in 59% (58% of which were negative)

• If cultures obtained after ABX onset: 71% were negative)

• Most frequently prescribed antibiotic: quinolones (18%)

• Pip/Tazo and or Vancomycin (22%)


Results

• Factors associated with de-escalation



Interventions to improve antimicrobial use

• Multifaceted, continuous educational approach to disseminate an up-to-date internal guideline adapted from published guidelines for management of intra-abdominal infections (IAI)

• Surgical unit at a tertiary care teaching hospital in Hamilton, Ontario, Canada

Popovski Z, et al. J Antimicrob Chemother. 2014.


• IAI are very common and are associated with high rates of morbidity and mortality


Why intrabdominal (IAI) infections?

• IAI often need treatment with broad-spectrum antimicrobials

• Guidelines highlight the importance of risk stratificationand local susceptibility patterns to guide empirical treatment

• The availability of clinical practice guidelines does notnecessarily change practice

A) Local consensus process to develop a guideline

Intervention

• Multidisciplinary team: ID, Micro, epidemiologists, surgeons

• items: empiric ABX, duration, iv to po switch

• Risk stratification:

Non-complicated communitiy acquired: ceftriaxone + metronidazole

Complicated* communitiy acquired: Piperacillin/Tazobactam

HA-IAI: Piperacillin/Tazobactam

* Previous ABS, comorbidity, APACHE >15

B-lactam allergic: ciprofloxacin + metronidazole



A) Local consensus process to develop a guideline

Intervention(ii)

• Endorsed by hospital and programme leadership

B) Guideline implementation

• Multimodal educational and collaborative approach (Dec´10-Mar´11)

1) educational tools: handouts, posters and pocket cards

2) providing educational sessions/meetings

• ID, surgery, pharmacists, nurses• Rotating residents at the surgery ward (beginning)



Baseline(preintervention)

Design. Patients

• “Pre-Post intervention quasi-experimental design”*

April ´10 Nov ´10 Jan ´11 Dec ´11

*Interrupted time series?

Postintervention

Patients were included if hospitalized in the surgical ward and: • IAI (appendicitis, cholangitis, cholecystitis, diverticulitis,

peritonitis, intra-abdominal abscess or perforation) • or if receiving pre-emptive antibiotics for intra-abdominal

trauma



Baseline(preintervention)

Analysis. Variables

• “Pre-Post intervention quasi-experimental design”*

April ´10 Nov ´10 Jan ´11 Dec ´11

*Interrupted time series?

Postintervention

Outcome variables

1. % patients with ceftriaxone/% patients withfluoroquinolones

Primary

2. DOT¥/1000 patient-days∞

¥Days of therapy∞ All patients in the study ward

Secondary

1. Duration of therapy

2. Clinical outcomes: mortality/readmission



ResultsBaseline: 512 antimicrobial regimens (152 unique patients)

Intervention: 484 regimens (145 unique patients)



Results

In DOT/1000 PD, there was a decrease in:

• Ciprofloxacin: from 221 to 74 (OR 0.3, 95% CI 0.2–0.3; P,0.001)

• Piperacillin/tazobactam: from 116 to 67 (OR 0.6, 95% CI 0.5–0.7; p 0.001)

• Cefazolin: from 49 to 38 (OR 0.8, 95% CI 0.6–1.0).

• Metronidazole: from 266 to 207; OR 0.7, 95% CI 0.6–0.8; p<0.001)

• The rate of ceftriaxone use increased from 6 to 92 (OR 17, 95% CI 10–25;




Results


• However, there is often a reluctance to de-escalate these broad-spectrum antimicrobials once they have been initiated

Lew KY. J Antimicrob Chemother. 2014 Dec 3.

• Carbapenems are appropriate empirical therapy in patients with moderate to severe infections and risk factors for infection with MDR Gram-negative organisms

• These concerns may be legitimate given the paucity of data in settings where Gram-negative resistance is endemic



• 1500-bed Taiwanese academic hospital (ASP est. in 2009)

Setting

• ESBL producers: 29% E. coli; 40% K. pneumoniae of all isolates cultured in the microbiology lab

• The ASP team comprises 4 ID physicians on rotation (making up 0.5 full-time equivalents daily) and 3 ASP pharmacists.

• Cases are reviewed every working weekday (8am to 5pm) from the day of carbapenem initiation.

a) Days 1 & 2 by the ward pharmacists for appropriate indications and dosage (institutional guidelines)

b) From day 3: Ward pharmacists and ASP team for a de-escalation opportunity based on clearly defined criteria



Setting (ii)

Day ≥3

Institution-approved guideline

Switch to otherantimicrobials as per empirical therapyinstitutional guidelines



• Feedback are made to the primary care team where appropriate.

Setting (iii)

• All recommendations are communicated to the primary care team through documentation in the patient’s chart and frequently include telephone or in-person discussions.

• Cases where the primary care team does not accept the ward pharmacist’s recommendations or the case is complicated are referred to the ASP team



• All patients receiving meropenem or imipenem from September 2011 to December 2012, for whom a recommendation for de-escalation was made

Patients

• Patients who received ≥1 course of were only includedonce

• Ertapenem was excluded as it is a narrower spectrum carbapenem recommended for the de-escalation from imipenem or meropenem


Primary outcome

Outcomes. Definitions

Proportion of patients who achieved clinical success

Clinical success: When all of the following criteria were met at 7 days after the ASP recommendation for de-escalation:

(i) the patient was alive(ii) there were no positive microbiological results(iii) the patient did not require a readministration of carbapenem or the addition of

other antimicrobials(iv) the patient still met the criteria for de-escalation

Secondary outcomes

• Duration of carbapenem use• Duration of antimicrobial therapy• Length of hospitalization,• Survival at hospital discharge• 30 day mortality from the start of treatment with the carbapenem• Readmission to hospital due to infection within 30 days.• Adverse effects

Outcomes were compared between those patients in whom de-escalation recommendations were followed andthose in whom not

Results: flowchart

Imipenem/meropenemcourses reviewed

(2433)

De-escalation recommendations

(428; 17.6%)Randomized to study (300)

De-escalation accomplished(304; 68%)

De-escalation ignored(96; 32%)

% to improve?Conservative approach?NNR (number neededto review)!!!

Any thoughts?

Why? Convenience?

Time-frame?

Results (ii)• No differences in patients´demographics, comorbidity, severity of

illness and type of antimicrobial therapy (empiric vs targeted)

Results (iii)

Results (iv): OutcomesPrimary outcome Proportion of patients who achieved clinical success

Secondary outcomes

De-escalated Non de-escalated

183/204 (89.7%) 85/96 (88.5%)

De-escalated Non de-escalated

Duration of carbapenem use 6 (4–8) 8 (7 – 11); IC95 (-3 to -2)

Duration of antimicrobial therapy 9 (7–14) 9 (7–14)

Length of hospitalization 18 (9–35) 20 (9-40)

Survival at hospital discharge 173 (84.8) 79 (82.3)

30-day mortality 25 (12.3) 14 (14.6)

30-day readmission 15 (7.4) 8 (8.3)

Adverse effects 11/204 (5.4%) 12/96* (12.5%) ; p=0.037

*diarrea

Conclusions

• De-escalation of carbapenem is feasible, even in the absence of microbiological data

• An institutional de-escalation guideline could be of help

• A back-end approach with a high burden of prescriptions might not be an efficient approach (low-sensitive screening)

• A Front-end approach* (education/protocols/prescribing assistance) are likely to be complementary tools

*Involving the clinician

Gerber JS. JAMA. 2014 Dec 17;312(23):2569–70


• A score to evaluate ASP was developed

• The score comprised 2 main categories:

1. Structures: Staff/Automated surveillance software

2. Strategies: preauthorization/audit & feedback, education, guidelines, iv to po programmes, de-escalation of therapy, antimicrobial order forms

• Multiple regression analysis to correlate score with targeted AB use

Pakyz AL. J Antimicrob Chemother. 2015


Pubmed


Thinking out of the box

Meeker D. JAMA Intern Med. 2014 Mar 1;174(3):425–31.


Front-end Approaches to Antimicrobial Stewardship

Hamilton KW. Clinical Infectious Diseases. 2015

• Guidelines have focused on the creation of top-down or centralized processes (preauthorisation/antimicrobial restriction or postprescription audit and feedback)…BUT

1. Most hospitals have challenges in implementing centralized ASPs: lack of dedicated personnel/financial resources

2. This approach may fail to affect the many episodes of antimicrobial use not subject to scrutiny by the stewardship team

3. Feedback occurs subsequent to the prescribing process with an inherent lag between antimicrobial exposure and the provision of feedback

• Frontline providers* have opportunities to enhance AS

* multidisciplinary healthcare providers (eg, nurses, pharmacists, and physicians) that assume direct responsibility for the daily care of patients or patient care unit




How to get the principles of antimicrobial prescribing incorporated into daily prescribing practice?

…shifting AS from the primary responsibility of centralized ASPs to a more universal practice among primary healthcare teams/units.




1. Paperforms (policy) + Implementation strategy

…and present their pilot experience with an antimicrobial flowsheet

Authors review several original papers on the topic

Thakkar J. J Antimicrob Chemother 2011; 66:1916–20

2. Check-list (policy) + Implementation strategyFleet E. J Antimicrob Chemother 2014; 69:2265–73

3. Electronic Medical Records (#EMR)





Wenzler E. Clinical Infectious Diseases. 2015

• Point-of-prescription interventions with frontline healthcare providers have the potential to expand existing ASPs and provide alternative approaches to performing stewardship at institutions without ASPs

• If we are to rely on prescribers a 2-tiered approach may need to be considered:

1. To create a robust antimicrobial stewardship effort that involves a multifaceted approach built around core strategies that do not rely solely on physician practices

• Knowledge and perceptions of prescribers about infections, antimicrobial prescribing and resistance are far from optimal




Wenzler E. Clinical Infectious Diseases. 2015

• If we are to rely on prescribers a 2-tiered approach may need to be considered:

1. To create a robust antimicrobial stewardship effort: multifaceted approach built around core strategies that do not rely solely on physician practices

• Point-of-prescribing intervention could supplement an existing ASP or be a strategy for performing stewardship in hospitals without an ASP

2. To develop a program to allow antimicrobials to be prescribed only by those physicians who are certified within an institution and have demonstrated the necessary education and competency to truly understand the risks and complexities associated with antibiotic use

• Analogous to those proposed by the Institute for Healthcare Improvement, The American Society of Clinical Oncology, and the American Society of Health-System Pharmacists to ensure the safe and effective prescribing of chemotherapeutic agents


Antimicrobial Stewardship (PROA) Journal Watch

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