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:
For treatment of Ertapenem-susceptible Gram-negative bacteria resistant to other beta- lactam antibiotics or/ and fluoroquinolones (and not Pseudomonas spp.) or/ and
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:
Severely ill neutropenic hemato-oncologic patients
Severely ill patients with pneumonia/acute respiratory distress syndrome (ARDS) who
may have suspected infection with Burkholderia pseudomallei
Severely ill patients with intra-abdominal sepsis
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
Known colonization with cephalosporin-resistant (e.g. ESBL) Gram-negative organisms (e.g. hemato-oncologic patients with mucositis or typhlitis)
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
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.