antimicrobial stewardship: media and literature update

Antimicrobial Stewardship (PROA): Media and Literature Update

José Ramón PañoServicio de Enfermedades Infecciosas

Hospital Clínico Universitario4 de octubre de 2016

Method: surveillance

• Lancet ID• CID• JAC• CMI• OFID• EIMC

• @PROA_HCUZ• @PROA_HULP• @ESGAP_ABS• @joserrapa

Outline• Antimicrobial stewardship in the political agenda

• New antimicrobials: how to promote its development

• Overall assessment of the impact of AMS programs

• “Shorter is better” (Apropos of CAP)

• Reported b-lactam allergy: more room for improvement than expected?

• AS from the Microbiology Lab

1. ECDC Draft Technical Report: July 2016

2. Open to public consultation: (Sept, 5th)

3. Draft Guideline: (Oct, 21st)

See here

https://proantibioticos.com/2016/08/24/guias-europeas-sobre-uso-prudente-de-antibioticos-abierto-el-periodo-de-consultas-hasta-el-5-s/

Proposal for EU draft guidelines: technical report or wish list?

Proposal for EU draft guidelines: technical report or wish list?

• Ensure timely access to clinical microbiology laboratory services. For acute care hospitals, these services should be provided on a 24/7 basis for critical specimens [expert consensus]

• Salary support and dedicated time for antimicrobial stewardship activities. Example: 0.5–1.5 full-time equivalents (FTEs) per 250 acute care beds [15,16]. Example of indicator: number of FTEs for antimicrobial stewardship activities.

3. Healthcare facilities (resources, systems and processes for healthcare facilities)

Nosotros, Jefes de Estado y de Gobierno y representantes de los Estados y Gobiernos, reunidos en la Sede de las Naciones Unidas en Nueva York el 21 de septiembre de 2016 (…)

(…) Por consiguiente, nos comprometemos a trabajar en los planos nacional, regional y mundial para: (…)

(…) b) Movilizar financiación suficiente, previsible y sostenida, recursos humanos y financieros e inversiones por conducto de canales nacionales, bilaterales y multilaterales para apoyar la elaboración y ejecución de planes de acción nacionales, la investigación y el desarrollo sobre antimicrobianos nuevos (…)

New antimicrobials: how to promote its development

“The findings support a form of a de-linkage model and a combination of push and pull incentive

mechanisms”

Clinical Infectious Diseases. 2016 Aug 30


Sales-revenue de-linkage model


• De-linkage model: Companies not paid on sales volumes, but by established revenues (flat rates)

• Companies strive for high sale volumes to improve their ROI, which can increase overuse of antimicrobials and can contribute to resistance emergence.

- Allow R&D investments for a successful product w/o requiring high product sales and could be adapted to simultaneously address conservation



Push incentives subsidize the overall development cost

Pull incentives reward successful development, providing guaranteed return on investment (ROI)

• Tax credits• Direct funding of research• Public–private partnerships

• milestone or prize payments• patent buyouts• advanced market commitments• and value-based or high reimbursement• regulatory incentives

Objective: To describe implementation of AS activities in 47 Southafrican private hospitals

Setting:• Private hospitals operated by NetCare (7/9 SA regions)

• 64 pharmacists (employees) y 4290 médicos (self-employees)• 9424 beds (ICU: 1601)

• ID scareceness

Intervention (2009-2014):- 3 phases: pre, implementation y post-implementation

Phase I Preimplementation: 16 months

- Result indicators:

- Process indicators1. Omission of blood cultures before starting antimicrobials2. > 7 days duration in the absence of indication (local guideline)3. > 7 days duration in the absence of indication (local guideline)4. Simultaneous use of ≥ 4 antimicrobials5. Redundant coverage

- Approach: Quality improvement (IHI)

I.1. Define goals and indicators

1. Global antimicrobial consumption2. Implementation

Brink A. Lancet Infect Dis. 2016;16(9):1017–25.


Fase I Preimplementation (16m)

I.2. AS model design• Non-restrictive (preserving prescribers’ autonomy) -> audit &

feedback: detection-review-feedback1-registry-feedback2

• Backbone = PharmD -> Voluntary involvement (no monetary involvement)…but dedicated time

I.3. “Champions” (PharmD) recruitment

I.4. Assessment of baseline situation (survey)

• Set-up of an AS multidisciplinary committee

• Implementation (speed) adapted to institution circumstances


Fase II Implementation(24 m)

Fase III PostImplementation(20m)

• Fase II: 31 learning cycles• Fase III: AS as “standard of care” (22 cycles)

Results (i): Antibiotic consumption


Results (iii): Process indicators


Results (iv): process indicators

Interventions: 7934 (6.8%)Period: 24m (730 d)Hospitals: 47

Interventions hospital/day*: 7934/34310 = 0.21*

Pacients receiving antibiotics: 116.662

Conclusions• Non-restrictive AS approach based on prescribers’

involvement with PharmD as program leader -> significant impact in antimicrobial consumption (SA)

• How much of the results are due to audit & feed-back? (reduced number of time-consuming interventions)

• Patient outcomes? Antimicrobial resistance?


• Población: Adultos ingresados con NAC* en 4 hospitales vascos

*NAC: nuevo infiltrado + 1 síntoma (fiebre / tos / disnea / dolor torácico)

• Período: Enero 2012 a agosto 2013

Uranga A. JAMA Intern Med. 2016 Jul 25.

Criterios de exclusión

• Inmunosupresión

• Riesgo de patógenos resistentes

Trasplante de órgano sólidoPrednisona > 10mg/día x 30 días u otros inmunosupresoresEsplenectomíaNeutropenia

InstitucionalizaciónIngreso en los últimos 15 díasUso de antibióticos sistémicos en los últimos 30 días

• Existencia de criterios de duración prolongadaInfección por P. aeruginosa o S. aureusComplicaciones locales o a distancia


Diseño• Screening: Días 0-5: comprobar criterios inc/excl

• Aleatorización: día 5

- Máxima Tª 48h: 37.8ºC- ≤ 1 criterios de estabilidad clínica

TAS < 90mmHgFC > 100/min,FR > 24 /minSatO2 < 90%, o PaO2 <60 mm Hg (aire ambiental)

- Intervención: suspensión AB* el día 5 - Control : duración AB* según criterio clínico

*AB : antibiótico elegido por el médico responsable


Variables resultado

A) Variables principales:• Buena evolución clínica (d10 y d30): Resolución o mejoría

de los síntomas de neumonía sin reintroducir antibiótico

• Síntomas NAC (d10 y d30): Cuestionario validado

B) Variables secundarias:

• Duración de tratamiento antibiótico (días): desde la primera dosis hasta el día 30

• Tiempo hasta mejoría/vuelta a rutina/resolución Rx

• Mortalidad (30 d)• Recurrencia NAC

Resultados

Resultados Características basales de grupos de intervención y control: equilibradas

AB: 80% quinolona

ResultadosVariable Control Intervención p

Buena evolución clínica (ITT) d10d30

48.6%88.6%

56.3%91.9%

0.180.33

Buena evolución clínica (PP) d10d30

50.4%92.7%

59.7%94.4%

0.120.54

Síntomas CAP (ITT) d10 d30

24.718.6

27.217.9

0.100.69

Síntomas CAP (PP) d10d30

24.618.1

26.317.6

0.160.81

Tiempo con antibiótico mediana (p25-p75)

10 (10-11)

5 (5-6.5)

< 0.001

Pacientes tratados 5 d 4 (2.9%) 101 (70.1%) <0.001

Tiempo hasta mejoría clínica 12 (8-18) 12 (7-15) 0.41

Recurrencia (día 30) 6 (4.4%) 4(2.8%) 0.53

Reingreso (día 30) 9 (6.6%) 2 (1.4%) 0.02

Resultados

Conclusiones/discusión

“Our study indicates that the IDSA/ATS recommendations for shorter duration of antibiotic treatment based on clinical stability criteria can be safely implemented in hospitalized patients with

CAP, leading to a significant reduction in treatmentduration.”

Fortalezas: • Estudio pragmático (vida real) con buen diseño y variables

relevantes

Limitaciones: • Extrapolación a determinadas poblaciones

1. b-lactámicos2. Fine V3. Atención a criterios de exclusión

• Reported allergy to b-lactam antibiotics is common and often leads to unnecessary avoidance in patients who could tolerate b-lactam therapy.

• Majority of reported prior reactions are misclassified as allergies

• Moreover, many individuals with true prior immunoglobulin (Ig) E–mediated reactions have loss of hypersensitivity over time

• Hypothesis: receipt of alternative therapy when a b-lactam agent is the preferred therapy leads to worse clinical outcomes

MacFadden DR. Clinical Infectious Diseases. 2016 Ahead of print

“Trainee-led* prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by an infectious

diseases consultation service at 3 academic hospitals”


*Infectious diseases residents developed and initiated the study as the initial phase of a division-wide, trainee-led quality improvement initiative

Methods (ii)

Study population: All inpatients seen in consultationby ID service (Apr 2014-Jan 2015) on days that the ID residents were present** for the review of cases.

**both weekdays and weekends. Routinely absent for 1 half-day per week of scheduled teaching), without other systematically excluded days.


Methods (ii)Prospective assessment of b-lactam allergy:• During consultation review rounds• Characterization of previous allergic reaction in:

- High risk: IgE-mediated (urticaria, bronchospasm, angioedema, or anaphylaxis), Stevens Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], and DRESS

- Low risk: rash, serum sickness, others

Preferred and chosen antibiotic therapies• Determined by the consultant ID service based on the initial

patient presentation and assessment

Review of patient outcomes• After the initial assessment, using comprehensive EMR• Quality control: 7 covariates; random 10% pts; k:0.94 + 2 ID doc

Results

Reported b-lactam allergy95 (19%)

Rececived b-lactam 47 (65%)

Didn’t receive b-lactam 25 (35%)

History of severe reaction48%

Patients included507

b-lactam preferred agent72 (76%)

History of severe reaction15%

P = 0.004


Results (ii)

CharacteristicNo

reported allergy

Reported allergy but b-lactam non preferred

Reported allergy and b-lactam preferred

Received preferred AB

Did not receive

preferred AB

N (507) 412 23 45 27

Inmunocompromised 72 5 9 3

Reported allergy description

IgE mediated 7 7 11Other severe 0 0 1

Rash 9 15 9Unknown 7 25 4

Results (iii)

CharacteristicNo

reported allergy




Did not receive

preferred AB

Antibiotic administeredPenicillin 45 0 7 0

Ceph 124 0 22 1BL/BLI 101 0 8 1

Carbapenem 34 1 10 3FQ 22 5 0 8

Clindamycin 1 1 0 5Glycopeptide 50 12 0 5

Aminoglycoside 3 1 0 1

Other 32 3 0 1

Results (iii)

CharacteristicNo

reported allergy




Did not receive

preferred AB

Site of infectionBacteremia (primary) 59 4 14 4Skin and soft tissue 54 3 7 5

Bone/Joint 53 5 5 2Gastrointestinal 60 5 5 4Genitourinary 52 2 5 5

Pulmonary 56 2 8 4

Results (iv)

CharacteristicNo

reported allergy

Reported allergy but b-lactam

non preferred



Did not receive

preferred AB

Primary outcome: Readmission + C. difficile + drug reaction + Acute kidney injury 67(16%) 5(22%) 11(21%) 10(40%)*

Secundary outcomeReadmission 24 (6%) 1(4%) 2 (4%) 6(24%)*

CDI 18 (4%) 1 (4%) 0 0Drug reaction 2 (0.5%) 0 4 (9%)* 2 (8%)+

AKI 29 (7%) 3 (14%) 5 (11%) 4 (16%)Mortality 55 (13%) 1 (4%) 10 (21%) 2 (8%)

Multivariate analysis

Primary outcome 3.18 (1.28–7.89)

Patient outcomes: univariate analysis

*p< 0.05

Conclusions

• “Reported b-lactam allergy was common and led to a significant proportion of patients receiving alternative antimicrobial therapy.”

• “Avoidance of preferred b-lactam therapy was associated with increased adverse outcomes (mainly readmission and adverse reactions that required discontinuation of therapy).”

• The risk of antibiotic-related reactions that required discontinuation of therapy was higher among patients carrying a label of allergy, regardless of whether or not they received beta-lactam

Conclusions (ii)

• There is a significant need to develop formal models of care within infectious diseases practices in order to objectively assess reported b-lactam allergies and optimize b-lactam use among patients without IgE-mediated allergy or other serious reactions.

• There is need to introduce self-audit skills and practice improvement and resource stewardship at the trainee level.

Limitations

• Selection bias (referral)- Frequency of ABX allergy

- Complexity of patients (maximum benefit of optimized therapy)

• Questions

- No aztreonam prescribed? How was it considered (preferred/non-preferred?

Dietz J. Am J Infect Control. 2016

• “62% of the patients had urine culture completed without specific symptoms of urinary tract infection”

• Starting in April 2006, the facility automatically started sending urinalyses with + nitrite or leukocyturia (≥8 WBC) for culture.

• Laboratory policy was changed in September 2014 to remove the reflex urine cultures and instead require providers to o

• The patient’s urine sample is held in the laboratory for 3 days to allow for urine culture to be added. A message was also added to the laboratory results for all urinalysis and urine cultures

Langford BJ. J Clin Microbiol. 2016 Aug 24;54(9):2343–7

Antimicrobial Stewardship in the Microbiology Lab: Impact of Selective Susceptibility Reporting on Ciprofloxacin Utilization and

Gram-Negative Susceptibility in a Hospital Setting

• A selective reporting policy was implemented which involved the suppression of ciprofloxacin susceptibility to Enterobacteriaceae when there was lack of resistance to the antibiotics on the Gram-negative panel

• 400-bed community teaching hospital in Toronto, Canada

• On-site microbiology laboratory, with staff available during daytime and evening hours

• Problems with C. diff and FQ-resistant P. aeruginosa

antimicrobial stewardship: media and literature update

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