Discussion
The pharmacist-driven ASP group interventions in febrile neutropenic
patients showed a favorable effect on antibiotic appropriateness in our
study. We found higher antibiotic appropriateness in the pharmacist
intervention group than the control group (88.9% versus 51.1%,P <0.001). When providing empirical therapy, the
pharmacist-driven ASP group was more appropriate than the control group
which was different from a previous
study.16 We
believe that main reason for this discrepancy was that the previous
study evaluated only prescribed antibiotic appropriateness based on the
hospital guideline and described only antibiotics indicated for febrile
neutropenia but did not assess the appropriateness of dosage regimens
which was included in our assessment of appropriateness of prescribed
antibiotics.16,22 Moreover, our ASP implementation
provided daily review and feedback while the Madran et al study
implemented a hospital guideline and had only a weekly discussion with
the ASP team.16 Likely our study which provided more
frequent feedback improved the primary physicians’ compliance as noted
in a recent study.10 Furthermore, our result showed
that appropriate dosage regimens was more frequently found in the
pharmacist-driven ASP group than the control group (97.8% versus
88.7%, P =0.049). Our finding was similar to previous studies
that appropriateness was 6.5-fold higher in the pharmacist intervention
group then the control group.23 On the other hand,
appropriateness of antibiotic indication in the pharmacist-driven ASP
group resembled the control group as described in Madran et al
study.16 However, we also used current standard
guidelines and all of our patients had a high risk of febrile
neutropenia similar to the previous study.16
In documented infection evaluations, the pharmacist-driven ASP group had
greater appropriateness of prescribed antibiotics than the control group
(88.9% versus 64.4%, P =0.004). Our result was similar to
previous study in which more appropriateness was found in the
intervention group.16 Moreover, appropriate duration
of therapy was higher in the pharmacist-driven ASP group
(P =0.039). Our result was concordant with a previous study that
pharmacist-driven ASP could reduce the duration of antibiotic
therapy.24 However, appropriateness of antibiotic
indication was similar in both groups because our study divided the
category of appropriateness into microbial susceptibilities and
penetration of antibiotic to target site. If pathogens were identified
and antibiotics susceptibilities were reported, it could help physicians
to choose proper antibiotics. Since most pathogens in the control group
were ESBL-producing organisms, this might affect antibiotic
appropriateness because carbapenems are drugs of choice for
ESBL-producing organisms and choice of antibiotics was controlled by an
infectious diseases physician.25 In addition, overall
antibiotic appropriateness and proper duration of therapy in the
pharmacist-driven ASP group were also greater than the control group
when the source of infection was unknown (P = 0.039 and 0.066,
respectively) (supplementary data, Table 3S). However, total antibiotic
duration between two groups did not difference. The reasons for
prolonging antibiotic duration in intervention group were fungal
infection (e.g., invasive pulmonary aspergillosis and mucormycosis),
superinfection with MDR organisms, uncontrolled source of infection.
Although the result did not show any difference of antibiotic
appropriateness in case of known causative pathogens and source of
infection between the two groups, the pharmacist-driven ASP group tended
to use more proper antibiotics than the control group in terms of
indication, dose and duration (P =0.384, 0.833, and 0.872,
respectively) (supplementary data, Table 4S).
Nevertheless, our study did not show a difference in the 30-day
infectious diseases-related mortality between the two study groups. Our
patients tended to have longer neutropenia durations and higher CRE
infection rates in the intervention group which differed from a previous
study (16). As a result of rising CRE incidence in Thailand, our
patients were more likely to be infected with CRE than reported in a
previous study which might have affected the mortality rate in our
study.16,26-27 However, other ASP studies in febrile
neutropenic patients also showed no difference in mortality between two
groups as well.10, 28-31 Based on our multivariate
analysis, pharmacists should collaborate with other medical personnel
such as infectious diseases physicians to improve the 30-day infectious
diseases-related mortality in febrile neutropenic patients caused by
cytotoxic chemotherapy. This study supports the IDSA Guideline that ASP
team should be done by a multidisciplinary team to achieve successful
ASP implementation.5 On-site infectious diseases
specialist, including ID physician and pharmacist, can improve ASP
effectiveness in recent study.32 Hence,
multidisciplinary team would be beneficial for ASP implementation in
these specific population which data are limited such as febrile
neutropenic patient. Notably, although most of the febrile neutropenic
patients in our study were caused by cytotoxic chemotherapy, there are
some patients caused by hematologic abnormalities during diagnosis in
our study which also mentioned in previous study.33Furthermore, our study did not find any difference in length of stay in
both groups as has been noted in a previous study.10
Although our target antibiotics utilization in the pharmacist-driven ASP
group increased during study period which was similar to a previous
study, it might have affected inappropriate prescriptions in the control
group.10 For instance, there were some antibiotics
improperly used in empirical therapy in the control group such as
ceftriaxone which were not included in our target antibiotics and
antibiotics might have been prescribes at an improper low dose.
Therefore, DDD of target antibiotics in the control group might be lower
than expected. Moreover, we implemented a high dose of target
antibiotics according to previous pharmacokinetic studies this might
have contributed to higher DDD of target antibiotic in the
pharmacist-driven ASP group.2-3 Besides, overall
intravenous antibiotics in the pharmacist-driven ASP group demonstrated
a lower trend than the control group.
Our study had several limitations. First, ward physician rotation could
have affected the result. However, the result of this study also showed
that the pharmacist intervention group had more appropriateness than the
control group. Second, the study was implemented only in medical wards
since TUH did not have a hematology-oncology ward during the study
period and we could not fully perform interventions in the other wards
such as the emergency department and intensive care unit. Ideally, the
ASP implementations in febrile neutropenic patients should be done in
all wards. Third, we calculated our sample size to demonstrate
antibiotic appropriateness rather than 30-day infectious
diseases-related mortality. A larger sample size is needed to assess the
effect of pharmacist-driven ASP on 30-day infectious diseases-related
mortality. Fourth, we could not evaluate the effect of pharmacist-driven
ASP on antibiotic resistance since the study site did not have an
isolation ward for febrile neutropenia patient with multidrug-resistant
pathogens. Thus, acquisition of antibiotic resistance organisms from
other patients might have affected our results. Finally, the role of
pharmacists in Thailand may be different from western countries.
Pharmacists cannot change antibiotic dosage regimen or discontinue
antibiotics by themselves, a physician’s signature is needed. Thus,
pharmacist cooperation with physician was also an important aspect to
implement a successful pharmacist-driven ASP in Thailand.