impact on prescribing through collaboration with an on-site
clinical pharmacy service
Introduction
The healthcare system relies on diligent antimicrobial prescribing.
Inappropriate antimicrobial prescribing has the potential to cause
significant harm. In addition to concerns for patient safety and
clinical outcomes, inappropriate use of antimicrobials contributes to
the emergence of drug resistance, affecting the overall health and
economics of our society.1 It is estimated that by
2050, 10 million lives a year may be at risk due to the rise of
drug-resistant infections.2 Promoting the appropriate
use of antimicrobials by coordinated and strategical Antimicrobial
Stewardship (AMS) Programs is a critical strategy to minimising the
emergence and spread of resistance.
AMS describes many activities; drug selection, dose, duration of therapy
and route of administration, that maximise appropriate use and minimise
the potential for antimicrobial resistance. Essential elements and
strategies for successful AMS programs in the Australian healthcare
systems include; providing access to clinical guidelines, implementing
formulary restrictions and approval systems, reviewing antimicrobial
prescribing with direct feedback to the prescriber as well as monitoring
antimicrobial use and outcomes and subsequently reporting this
information to clinicians and management.3
While the concept of stewardship was first introduced in the
1970s,4 its worldwide acceptance and uptake has been
slow. In 2007, the Infectious Diseases Society of America and the
Society for Healthcare Epidemiology of America published guidelines for
the development of AMS programs.5 In 2011, the
Australian Commission on Safety and Quality in Health Care (ACSQHC)
recommended AMS programmes be established in all Australian
hospitals,6 and their implementation became part of
the National Safety and Quality Health Service Standards for
accreditation of all hospitals, including regional and rural facilities
in 2013.7
Despite the implementation of policies and procedures for effective AMS
programs, studies describing AMS success within Australia have
demonstrated differences in the number and level of activities
performed; particularly in remote and rural
Australia.8-10 Australia’s first National
Antimicrobial Resistance Strategy was released in
2015,11 leading to the establishment of a surveillance
program by the ACSQHC. The first national report from the Antimicrobial
Use and Resistance in Australia (AURA) project was released in June 2016
and included appropriateness data from the 2014 National Antimicrobial
Prescribing Survey (NAPS). This report found antimicrobial use in
Australian hospitals to be moderately high when compared to similar
countries.12
Barriers to the effective establishment of Antimicrobial Stewardship
Programs (AMS) in rural and remote hospitals have been recently
reported.8-10,13-15 These include; culture of
independence and self-reliance by local clinicians, lack of resources
including access to on-site Infectious Disease (ID) Physicians,
inadequate feedback on institutional prescribing patterns, and inability
to meaningfully benchmark performance.13 However,
despite these challenges, evidence of successful implementation of AMS
initiatives have been published. In the absence of an on-site ID expert,
models of care such as pharmacist, nurse, or externally-led initiatives
as well as the use of telehealth, visiting ID specialists can be
successfully implemented.9,16
Pharmacists play a central role in reviewing and monitoring
antimicrobial prescriptions, implementing restricted formulary listings,
providing education and feedback to clinicians, and are therefore
ideally placed to influence prescribing practices. Pharmacist
involvement in AMS programs is therefore recommended as a component of
the multidisciplinary approach to promoting appropriate antimicrobial
prescribing.6,17
Port Lincoln Health Service (PLHS) Pharmacy Department is a new service
which was established by SA Pharmacy and Country Health South Australia
(CHSA) in November 2016; and provides a range of services including
dispensing, clinical ward service, preadmission clinic and chemotherapy
as well as supporting smaller hospitals across the Eyre Peninsula and
West regions. There is currently no easily accessible data that
evaluates the effect of the CHSA AMS program at PLHS.
The objectives of this study were to i) describe the impact of clinical
pharmacy services on antimicrobial prescribing at a small rural General
Practitioner (GP)-led hospital in Port Lincoln, South Australia, ii)
explore areas of suboptimal antimicrobial prescribing for further
improvement, and iii) review of total antimicrobial cost per patient day
pre- and-post implementation of clinical pharmacy services.
The study was approved by the Central Adelaide Local Health Network
Human Research Ethics Committee (HREC/18/CALHN/611; R20180902).
Methods
A retrospective case series audit of ID cases was conducted, to compare
and assess the appropriateness of antimicrobial therapy pre- and-post
implementation of clinical pharmacy services at a local rural GP-led
hospital in Port Lincoln, South Australia (SA).
PLHS is a 50-bed hospital in the Eyre and Western Health Services in SA
with an Australian Statistical Geography Standard (ASGS) remoteness
classification of “remote”. The hospital includes an Emergency
Department, Special Care Unit, collocated Chemotherapy and Renal
Dialysis and Operating theatre facilities and two general wards. Medical
patients are managed by local GPs from three clinics in Port Lincoln
(nominally Clinic A, B and C for this study). The Emergency Department
is led by a rotating roster of local GPs and locum doctors when
required. The hospital serves as training sites for medical students,
surgical and GP registrars. The hospital provides surgical care to
patients and hosts several permanent as well as visiting surgical
specialists.
In the last five years, a network of Antimicrobial Stewardship Programs
across CHSA has been implemented. Specialist ID consultation is not
available on-site; however ID specialists can be contacted for advice if
required via a metropolitan hospital.
All adult patients who presented to PLHS with the following infectious
pathologies; sepsis, febrile neutropenia, cellulitis, urinary tract
infections (UTIs) and community-acquired pneumonia (CAP) between May and
August 2015 and repeated for same period in 2018 were included in the
study. The infectious pathologies were selected based on both being a
common admission cause and also having clear guidelines existing for
management. Cases were identified via ICD codes on the patient medical
records with the diagnoses determined (and assumed correct) as
documented by the treating physicians.
Figure 1 describes patient exclusion criteria for this study.
De-identified data were collected and collated in a Microsoft
Excel® 2010, (Version 14.0.7229.5000) document and
saved on a secured server of SA Pharmacy network. Data were collected
using the standardised CHSA Local Health Network AMS Audit Tool, adapted
to include the following details: patient demographics, indication for
antimicrobial therapy, clinical observations and results of blood and
culture tests, drug name, dose, route, frequency, duration (number of
doses), cost of therapy, hospital length of stay, whether infectious
disease or microbiology expert advice was sought, history of the adverse
antimicrobial event, number of missed doses, therapy not prescribed, GP
practice and prescriber details.
The severity of disease was assessed by the principal investigator for
the appropriateness of therapy as per the Therapeutic Guidelines
(15th edition, 2014), as follows:
The severity of CAP was assessed using the SMART COP and CURB65 scores
(tools for assessing severity of CAP). Severe cellulitis was defined as
patients who had significant systemic features or not improving after 48
hours of oral therapy. For UTIs, asymptomatic, uncomplicated cystitis or
mild pyelonephritis (low grade fever, no nausea or vomiting) were
classified as mild, and complicated cystitis or severe pyelonephritis
were classed as severe infections. Sepsis was defined as infection,
either suspected or confirmed, with systemic features such as fever,
tachycardia, tachypnoea or elevated white cell count. SIRS and qSOFA
scores (tools for assessment of severity of sepsis) were calculated for
patients with a documented diagnosis of sepsis, and antimicrobial
therapy was assessed for both empirical as well as directed therapy
where infection source was or became apparent during the patient
admission. Assessment of febrile neutropenia was based on clinical
suspicion or likelihood of febrile neutropenia (neutrophils less than
0.5 × 109/L, or less than 1 × 109/L
with a predicted decline to less than 0.5 × 109/L, and
fever 38ºC or higher in an immunocompromised patient).
Appropriateness of antimicrobial prescriptions was assessed by the
principal investigator, according to the National Antimicrobial
Prescribing Survey (NAPS) guidelines. The antimicrobial order was
defined as; 1) optimal - if prescribed therapy follows either the
recommended therapy as per the Therapeutic Guidelines or locally
endorsed guidelines; 2) adequate - if it did not follow the Therapeutic
Guidelines but was a reasonable alternative choice for the likely
causative pathogen; 3) suboptimal - if it was an unreasonable choice for
the likely causative pathogen including an excessively broad spectrum of
cover or unnecessary overlap in spectrum of activity, and 4) inadequate
- if therapy was unlikely to treat the causative organism or if
antimicrobial therapy was not indicated.18
Optimal and adequate prescriptions were deemed “appropriate”, while
suboptimal and inadequate prescriptions were classified as
“inappropriate”.
Therapeutic Guidelines Limited was contacted to confirm the use of
Antibiotic Therapeutic Guidelines 15th edition was
appropriate for this study as it was released in 2014; with no change in
guidelines between 2015 and 2018.
Costs were assessed based on the average cost per patient day of
administered antimicrobials for the two groups. Cost comparisons were
based only on acquisition costs of antimicrobials as per the hospital
contract prices for 2015 and 2018. A comparison of cost (acquisition)
between appropriate and inappropriate therapy was also performed.
Parametric data were analysed using Student T-test and Chi-square test
for continuous and categorical data retrospectively. Non-parametric
continuous data were assessed using the Mann-Whitney U test, and p
< 0.05 was considered significant. Statistical analysis was
analysed using Microsoft Excel® 2010, (Version
14.0.7229.5000) and STATA (Version13 StataCorp, Texas, 2013)
Results:
A total of 273 antimicrobial prescriptions (1690 doses) from 110
eligible patient admission records were included in the study. The 2015
sample included 115 antimicrobial orders and the 2018 sample158. The
difference between the two groups in age, proportion of Aboriginal and
Torres Strait Islander (ATSI) patients included, severity of disease,
SMART COP scores, SIRS and qSOFA scores, percentage of patients from
each clinic and length of stay was not statistically significant. (Table
1)
A total of 86% (55/64) of patients in the post intervention group were
reviewed by a clinical pharmacist during their admission.
There was no statistically significant difference in the number of
patients admitted for sepsis (p=0.43), CAP (p=0.95) or UTI (p=0.14). The
increase in the proportion of patients treated for cellulitis in 2018
compared to 2015 was statistically significant (p=0.049).
There was a significant improvement in overall prescribing of
antimicrobial therapy at PLHS after the introduction of a clinical
pharmacy service (Figure 2). Appropriate therapy was increased from
66/115 (57%) in 2015 to 129/158 (82%) in 2018 (p=0.0013). Optimal
therapy was prescribed in 35% (40/115) of antimicrobial orders in 2015
and 68% (108/158) in 2018 (p=0.0015).
Appropriateness of antimicrobial choice was reviewed according to the
type of infection as well as prescriber clinic to identify possible
practice trends.
There was an improvement in the proportion of patients appropriately
treated for cellulitis (p=0.008) and CAP (p=0.015) in 2018. No
statistically significant difference in appropriateness of antimicrobial
prescriptions for UTI (p=0.14) and sepsis (p=0.35) was found.
There was more appropriate antimicrobial prescribing in 2018 compared to
2015 from both clinic A and clinic B prescribers (p=0.0086 and p=0.0004
respectively). No significant difference was seen in antimicrobial
prescribing patterns of clinic C and surgical patients (Other, p=0.15).
A total of 21 doses in 2015 and 5 doses in 2018 were found to have been
omitted or not given during the study (P=0.0002).
Ceftriaxone, benzylpenicillin and gentamicin were the top three
antimicrobials which were prescribed inappropriately in 2015 (n=14, 7
and 6 respectively), while in 2018 ceftriaxone was the main culprit for
inappropriate prescribing (n=12). Reasons for inappropriate prescribing
were most commonly wrong dose or inappropriate spectrum of antimicrobial
activity for the infection (Table 2).
The cost of antimicrobial therapy per patient day was halved from $10
and $5.33, pre and post introduction of clinical pharmacy service,
respectively. Cost of inappropriate therapy per patient day was reduced
from $6 in 2015 to $4.25 in 2018.
Discussion:
This study details significant changes to antimicrobial prescribing
patterns in a small rural GP led hospital in remote Australia, after the
implementation of a clinical pharmacy service. Optimal prescribing of
antimicrobials increased by 33%, while inadequate prescribing was
reduced from 18% to 5% in 2018.
Measuring the success of AMS interventions depends on the type of
activity and outcomes reviewed, and appropriate prescribing does not
necessarily lead to reduced antimicrobial use.19 By
quantifying the number of antimicrobials which are appropriately
prescribed, we were able to show an improvement in appropriate
antimicrobial orders.
Comparing the rates of inappropriate prescribing at PLHS with national
reported rates shows conflicting results. The 2017 Antimicrobial Use and
Resistance in Australia (AURA) report, which includes data collected
from NAPS 2015 and showed that 21.9% of all antimicrobial prescription
orders were assessed as inappropriate, and 23.3% not complying with
guidelines. An Australian review of antimicrobial prescribing between
Rural and Remote Hospitals (RRHs) and metropolitan hospitals by Bishop
et al. (2018),9 found a statistically higher rate of
inappropriate prescribing 23.91% vs 22.16% (p<0.001) in the
rural setting.13 The antimicrobial prescriptions
included in this review comprised of 2.27% from remote hospitals
according to the ASGS. The rate of inappropriate antimicrobial
prescribing at PLHS, however, was found to be significantly more
prevalent in 2015 (43%) and has since been improved considerably to
18%.
The reason for the significant rates of inappropriate prescribing in
2015 is unclear and may be multifactorial. The small sample size of this
study is a possible contributing factor. It may also be related to
sampling bias as Bishop et al9 utilised data from
NAPS, which is a voluntary survey. Therefore hospitals with limited AMS
involvement may choose not to participate.
In exploring areas of suboptimal prescribing, the results highlighted
that ceftriaxone was the most inappropriately prescribed antimicrobial
in the two arms of the study. This finding is consistent with the
literature around its use in RRHs.13,20 Overuse of
ceftriaxone may be associated with the emergence of resistant organisms
as well as the potential for Clostridium difficileinfections.20 Ceftriaxone was prescribed at
inappropriate doses and was an unnecessarily broad-spectrum choice for
most indications.
Additionally, the results show a significant cost saving related to
antimicrobials administered per patient day. Although the total
antimicrobial cost was reduced by half, it did not wholly reflect the
cost of inappropriate prescribing, which was only reduced by 30%. This
aspect is likely because appropriate therapy can also affect the cost.
The impact and effectiveness of pharmacist intervention on antimicrobial
prescribing has been well documented and
published.21-24 Clinical pharmacy interventions may
include patient-specific recommendations, implementation of policies and
formulary restrictions, education, feedback and therapeutic drug
monitoring.21 The implementation of all these
interventions by the new clinical pharmacy service in PLHS is likely to
have generated a significant impact on antimicrobial prescription
choices. Multifaceted and interdisciplinary approaches to AMS is more
effective than a single intervention21 and
recommendations made by a dedicated specialist ID pharmacist also has a
higher adherence rate than a ward pharmacist.24However, in the absence of specialist ID pharmacist, pharmacists with
drug utilisation skills are instrumental to the success of AMS
programs.19 As the PLHS pharmacy is part of a larger
organisation (SA Pharmacy), offsite collaboration and discussion with
specialist staff for complex cases can be implemented and contribute to
improved AMS on site.
There are a few identifiable limitations in this study. The first is the
retrospective design and the small sample size. Workforce capability and
capacity limited the potential for a prospective design and larger
sample size. The second is that appropriateness of the duration of
therapy was not assessed. Thirdly it was challenging to assess the
acceptance rate of the pharmacists’ recommendations retrospectively. The
lack of clinical pharmacist involvement in after-hours decisions and
limited documentation by the GPs on the justification for changes to
prescribing were the main limiting factors for failure to collect this
data.
Overall, our results provide baseline data for future benchmarking of
AMS activities in the region and allow us to implement strategies for
improvement of antimicrobial prescribing at a local level.
Overprescribing of ceftriaxone doses were found to be areas which will
benefit from additional education as a result of this audit. Discussion
with the clinicians regarding these findings will be instrumental in
transforming this practice in the future.