IMPACT OF A CARBAPENEM ANTIMICROBIAL STEWARDSHIP PROGRAM ON PATIENT OUTCOMES.

2017年 AAC に発表された、カルバペネムからのDe-escalationに関するASP報告。

Abstract

Antimicrobial stewardship programs (ASPs) aim to improve appropriate antimicrobials use. However, concerns of the negative consequences from accepting ASP interventions exist, particularly when de-escalation or discontinuation of broad-spectrum antibiotics are recommended. Hence, we sought to evaluate the impact on clinical outcomes when ASP interventions for inappropriate carbapenem use were accepted or rejected by primary providers.

We retrospectively reviewed all carbapenem prescriptions deemed inappropriate according to institutional guidelines with ASP interventions between July 2011 and December 2014. Intervention acceptance and outcomes including carbapenem utilization, length-of-stay, hospitalization charges, 30-day readmission and mortality rates were reviewed. Data was analyzed in groups where physicians accepted all interventions ("Accepted") versus rejected ("Rejected").

A total of 158 ASP interventions were made. These included: carbapenem discontinuation (35%), change to narrower-spectrum antibiotic (32%), dose optimization (17%), further investigations (including imaging, procalcitonin) (11%), Infectious Diseases referral (3%), antibiotic discontinuation (other than carbapenem) (1%) and source control (1%).Of 220 unique patients, carbapenem use was inappropriate in 101 (45.9%). Significant reduction in carbapenem utilization was observed in the "Accepted" group versus "Rejected" group (median defined daily doses: 0.224 versus 0.668 per 1000 patient-days, p<0.001). There was a significant reduction in 30-day mortality in "Accepted" (none) versus "Rejected" group (10 deaths, p=0.015) but there was no difference in length-of-stay, hospitalization charge and 30-day readmission rates. Hypotension was independently associated with mortality in multivariate analysis (odds ratio, 5.25, 95% confidence interval, 1.34-20.6).

In our institution, acceptance of carbapenem ASP interventions did not compromise patient safety in terms of clinical outcomes while reducing consumption.

ASP

In summary, the main strategy adopted by our ASP was a prospective-review-and-feedback approach based on IDSA recommendations.

A  list of active carbapenem orders was generated daily Monday through Friday.

Our ASP team, comprised of an Infectious Diseases physician and a full-time pharmacist, assessed appropriateness of carbapenem use based on our institutional guidelines for the respective clinical condition at initiation to the end of therapy.

Recommendations which detailed appropriateness of use or otherwise and clear reasons for our interventions were conveyed to the primary team via written documentation in case notes and verbal communication.

ASP interventions include:

1) discontinuation of carbapenem,

2) change to narrower-spectrum antimicrobial,

3) optimize dosing,

4) further investigations (including procalcitonin, imaging, cultures),

5) Infectious Diseases referral,

6) discontinue antibiotic (other than a carbapenem)

7) source control (e.g. line removal).

Intervention acceptance was reviewed by the ASP team the next working day to determine its acceptance or otherwise.

Reason(s) for non-acceptance were clarified by the ASP physician or the pharmacist with the primary team either via face-to-face or telephone conversations and documented.

There may be more than one intervention made for a patient.

Recommendations were reviewed throughout the individual’s entire carbapenem course in particular where new results such as culture(s) and/or further investigations such as procalcitonin, imaging were available.

Table 1. Criteria for appropriate use of carbapenem

1) Targeted Therapy
a. For treatment of serious cephalosporin-resistant e.g. Extended Spectrum Beta-Lactamases (ESBL) resistant Gram-negative infections
b. For second-line treatment of Gram-positive/negative infections in serious penicillin or cephalosporin allergy (e.g.: extensive rash, angioedema or anaphylactic reactions)
c. Ertapenem should only be used as targeted therapy or as de-escalation therapy from other broad-spectrum carbapenems when the following criteria are met:

1. For treatment of Ertapenem-susceptible Gram-negative bacteria resistant to other beta- lactam antibiotics or/ and fluoroquinolones (and not Pseudomonas spp.) or/ and

2. If patient is amenable to outpatient IM/IV Ertapenem antimicrobial therapy

2) Empiric Therapy

a. Empiric first-line therapy in severe/overwhelming sepsis (especially multi-organ dysfunction) requiring ventilatory and/or inotropic support for:

1. Severely ill neutropenic hemato-oncologic patients

2. Severely ill patients with pneumonia/acute respiratory distress syndrome (ARDS) who

   may have suspected infection with Burkholderia pseudomallei

3. Severely ill patients with intra-abdominal sepsis

4. Severely ill neonatal patients in Intensive Care Unit with signs of worsening sepsis

b. Empiric second- or third-line therapy for febrile neutropenic patients with strong evidence of cephalosporin-resistant Gram-negative infection

1. Known colonization with cephalosporin-resistant (e.g. ESBL) Gram-negative organisms (e.g. hemato-oncologic patients with mucositis or typhlitis)

2. Blood culture positive for Gram-negative bacteria before final identification and susceptibility testing. 

3) Prophylaxis (To discuss with ASP Physician/Pharmacist for prophylactic use)

a. Prophylaxis for major surgical procedures in a patient with serious penicillin and cephalosporin allergy
b. Prophylaxis for major surgical procedures in patients with pre-existing infections with cephalosporin-resistant Gram-negative bacteria at the site of surgery

limitations

We acknowledge that there are several assumptions and limitations in this single-center

observational study, where measures of metrics such as length of stay and mortality are subject to inherent biases due to secular trends in healthcare. However, these metrics do have their usefulness as a ‘balancing measure” to assure key stakeholders that ASP  interventions do not lead to increased harm or excessive mortality, in particular where efforts are focused on reduction in excessive prescribing. Also, our findings may not be entirely generalizable to other institutions where patient populations, ASP mechanisms and prescribing practices may differ. However, we hope to be able to address the impact of ASP interventions on compensatory antibiotic use and carbapenem-resistance in the future.

感想

カルバペネムからのDe-escalationによる死亡率低下とカルバペネム消費量の減少を示したごちゃっと報告。

患者背景の違いがあり、重症度の慎重な検討を望みます。

AACの報告って感じですね。