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| Journal of the New Zealand Medical Association,
15-April-2011, Vol 124 No 1332
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Antimicrobial consumption at Auckland City Hospital:
2006–2009
Rob Ticehurst, Mark Thomas
Increasing rates of resistance to widely used antimicrobial
medicines in common bacterial pathogens pose a growing health threat. Infections
due to these resistant pathogens frequently require treatment with medicines
which may need to be administered intravenously rather than orally, may be
associated with increased risk of toxicity, and may be less effective and more
expensive than previously used agents. In a small but worrying proportion of
patients the pathogen may be resistant to all available antimicrobial agents and
infections that previously were curable may have no effective
treatment.1
The major factor driving the evolution and spread of
antimicrobial resistance is antimicrobial use. A number of other factors, such
as demographic context (overcrowding, inadequate hygiene, etc), associated
illnesses (especially those that result in some immune compromise and/or
repeated hospital admissions) and failure to attend to hand hygiene,
immunisation and other measures intended to reduce transmission of infection
from person to person, also contribute to the spread of resistant microbes, but
in general are less important than antimicrobial use.
A large number of studies have demonstrated strong
associations between the volume of antimicrobial agents consumed and the rates
of resistance in common bacterial pathogens to commonly used antimicrobial
agents. Such associations have been seen at the level of the individual
patient,2 at the level of the hospital and its
surrounding community3 and at the national
level.4,5
The strong relationship between the volume of antimicrobial
agents consumed and the rate of resistance to many antimicrobial agents should
be a powerful motivating force to ensure that these agents are used wisely. Many
surveys have shown that antimicrobials are very frequently overused and there is
considerable potential for reductions in the volume of antimicrobials commonly
prescribed for a range of conditions.6
The type of antimicrobial commonly prescribed also has an
effect on the rates of resistance to antibacterial agents. Prescription of
antimicrobial agents with either a very broad antimicrobial spectrum or a low
genetic barrier to the development of resistance is associated with increased
rates of resistance in common bacterial pathogens.
Marked differences have been found between prescribing
patterns at the level of the individual doctor and at the national level.
Interventions intended to change the type of antimicrobial prescribed for
various infectious syndromes have been associated with reductions in the rate of
resistance in common pathogens.7–9
The hospitals of the Auckland District Health Board (ADHB):
Auckland City Hospital (ACH), Starship Children’s Hospital (SSH) and
Greenlane Clinical Centre (GCC), provide secondary healthcare to the residents
of central Auckland (approximately 450,000 people in 2009) and tertiary
healthcare to the wider Auckland region population (approximately 1,436,400
people in 2009) for some services (e.g. neurosurgery, ophthalmology, cardiac
surgery) and to the total New Zealand population (approximately 4,315,800 people
in 2009)10 for other services (e.g. liver,
heart and lung transplantation).
We have retrospectively measured antimicrobial consumption
within the ADHB hospitals during the years 2006–2009. We anticipate that
our results will provide a baseline for comparisons with other New Zealand
hospitals, and with future prescribing within the ADHB hospitals. We also
anticipate that the results will identify opportunities to encourage changes in
antimicrobial prescribing that might either slow or reverse the rising rates of
infection with resistant bacteria.
MethodsAll medications prescribed for inpatients of ACH, SSH
or GCC are purchased by the central ACH pharmacy. The computerised records for
antimicrobial dispensing from this central pharmacy were accessed for the years
2006 to 2009. The amount of antimicrobials dispensed in each of these years was
measured for each clinical unit involved in inpatient care.
Medications dispensed to patients within psychiatric
wards, outpatient clinics, day stay units, etc were not included. Antimicrobial
agents were aggregated into the following classes in accordance with the
Anatomic Therapeutic Chemical (ATC) classification: tetracyclines (J01AA),
penicillins with extended spectrum (J01CA), beta-lactamase sensitive penicillins
(J01CE), beta-lactamase resistant penicillins (J01CF), combinations of
penicillins, including beta-lactamase inhibitors (J01CR), first-generation
cephalosporins (J01DB), second-generation cephalosporins (J01DC),
third-generation cephalosporins (J01DD), fourth-generation cephalosporins
(J01DE), monobactams (J01DF), carbapenems (J01DH), trimethoprim and derivatives
(J01EA), intermediate acting sulphonamides (J01EC), combinations of
sulphonamides and trimethoprim (J01EE), macrolides (J01FA), lincosamides
(J01FF), other aminoglycosides (J01GB), fluoroquinolones (J01MA), glycopeptides
(J01XA), polymyxins ((J01XB), steroid antibacterials (J01XC), imidazole
derivatives (J01XD), nitrofuran derivatives (J01XE) and other antibacterials
(J01XX08).11
The total weight of each antimicrobial dispensed was
used to calculate the consumption using the defined daily dose (DDD) measurement
unit.11
The Information Management and Technical Services
department of the ADHB provided data on the total number of admissions and
inpatient days for adults admitted to ACH or GCC (ophthalmology inpatients
only), and for children admitted either to SSH or to the Neonatal Intensive Care
Unit (NICU) in ACH; and for adults admitted to: the Department of Critical Care
Medicine (DCCM:14 beds), the Cardiovascular Intensive Care Unit (CVICU:12 beds),
the four adult general medical wards (100 beds), the two adult general surgical
wards (50 beds), the adult haematology ward or the bone marrow transplant unit
(20 beds) and the adult liver and kidney transplant ward (34 beds). The number
of people resident within the area for which the ADHB provides secondary
healthcare was obtained from the 2006 census.10
These data were used to calculate annual rates of DDD/100 admissions, DDD/100
inpatient days and DDD/1000 inhabitants/day.
ResultsThe total monthly consumption of antimicrobial agents, and
the total monthly number of inpatient days, for adults admitted to ACH or GCC
(total 902 inpatient beds) and for children admitted to SSH or NICU (total 281
inpatient beds), during 2006 to 2009, are shown in Figure 1.
Overall, the total consumption of antimicrobials (measured
in adult DDDs/month) by adult inpatients was approximately four times greater
than that by paediatric inpatients. For both children and adults there was
relatively little variation in either the total monthly consumption of
antimicrobial agents or the total number of inpatient days between the winter
months (June, July, August) and the summer months (December, January,
February).
Figure 1. Total consumption of antimicrobial
agents (DDD) and total number of inpatient days for adult patients (ACH and GCC)
and for paediatric patients (SSH and NICU), by month during
2006-2009
 Note: In the absence of an accepted
method of measuring paediatric DDDs, the total monthly consumption of
antimicrobial agents by adult inpatients, and by paediatric inpatients, was
measured in adult DDDs.
Figure 2 shows the relative contribution made by each
inpatient unit to the total antimicrobial consumption by adult patients in ACH
and GCC during 2009. The emergency medicine department and assessment planning
unit (10%), the general medical wards (16%), the general surgical wards (9%) and
the care for the elderly and rehabilitation wards (7%) together consumed
approximately 40% of the total adult inpatient consumption. Between them the
DCCM and the CVICU were responsible for approximately 3% of the total adult
inpatient consumption.
The annual consumption of antimicrobial agents within ADHB
hospitals by antimicrobial class for the years 2006 to 2009 is shown in Table 1. The average annual increase in total antimicrobial
consumption during the four year period from 2006 to 2009 was approximately 3.2%
for DDD/100 admissions, approximately 2.7% for DDD/100 inpatient days and
approximately 4.3% for DDD/1,000 inhabitants/day.
Significant changes were apparent in the consumption of some
antimicrobial classes during the same four year period. The annual consumption
of carbapenems (measured in DDD/100 inpatient days) increased by approximately
50% in both 2007 and 2008 and then declined by approximately 20% in 2009. The
annual consumption of fluoroquinolones and of glycopeptides increased by
approximately 130% and 190% respectively in 2007 but the annual consumption of
both of these classes then declined over the next 2 years. Figure 2. Total
annual consumption of antimicrobial agents (DDD) by adult inpatients in the
various clinical units of ACH during 2009
 The annual consumption of antimicrobial agents by adult
inpatients in the general medicine wards, general surgery wards, liver and
kidney transplant ward, haematology ward, DCCM and CVICU, for the years 2006 to
2009 are shown in Figure 3. It shows that total antimicrobial consumption in the
general medicine, general surgery, and liver and kidney transplant wards was
relatively stable during this four year period (approximately 80–100
DDD/100 inpatient days), with low levels of consumption of some restricted
antimicrobials (third and fourth generation cephalosprins, carbapenems,
vancomycin and fluoroquinolones).
Relatively high levels of consumption of third and fourth
generation cephalosporins (approximately 60 DDDs/100 inpatient days), and of
glycopeptides (approximately 8 DDDs/100 inpatient days) were seen on the
haematology ward, where cefepime (a 4th
generation cephalopsporin) is a component of the empiric treatment of patients
with neutropenic fever, and vancomycin is commonly used in the treatment of
patients with intravascular cannula-related sepsis. An increase in the
consumption of carbapenems was seen in most wards during the four year period,
in response to an increase in the prevalence of infections due to extended
spectrum beta-lactamase (ESBL) producing Gram-negative bacilli.
Figure 3. Consumption of antimicrobial agents
(DDDs/100 inpatient days) in the general medicine wards (A), general surgery
wards (B), liver and kidney transplant ward (C), haematology ward (D), DCCM (E)
and CVICU (F), for the years 2006 to 2009
 Note: The y-axis is truncated in the
same manner for all six graphs.
DiscussionThis audit has shown that the total annual antimicrobial
consumption by adult inpatients within the ADHB hospitals during 2006 to 2009
was comparable to the average levels of inpatient consumption in Sweden, Norway,
Denmark, Ireland, and Israel during 2008. It was considerably less than the
average levels of inpatient consumption in hospitals in France and Italy during
2008 (Figure 4).12
Figure 4. Antimicrobial consumption (DDD/1,000
inhabitants/day) by class for adult inpatients in ADHB hospitals during 2008
compared with total national antimicrobial consumption for adult inpatients in
hospitals in Sweden, Norway, Denmark, France,
Ireland, Italy and Israel during
200812
 The approximately 3% annual increase in total antimicrobial
consumption by adult inpatients within the ADHB hospitals between 2006 and 2009
was comparable to that seen recently in Scandinavian hospitals. Total annual
antimicrobial consumption, measured in DDD/1,000 inhabitants/day, increased by
2.6% per year in Swedish hospitals between 2000 and
2008,13 by 7% in Danish hospitals between 2007
and 200814 and in Norwegian hospitals by 1.2%
between 2006 and 2007 but by 10% between 2007 and
2008.15
While the total antimicrobial consumption by adult
inpatients within ADHB hospitals was comparable with the relatively low levels
of consumption by adult inpatients in Scandinavian hospitals, the consumption of
antimicrobials within each class differed significantly. These differences are
clearly apparent with regard to penicillins, which comprised between 1/3 and 1/2
of the total adult inpatient antimicrobial consumption in the ADHB hospitals and
in most European countries during 2008 (Figure 4).
Beta-lactamase sensitive penicillins (predominantly
benzylpenicillin and phenoxymethylpenicillin) comprised a relatively small
proportion of the total penicillin consumption within ADHB or
Australian16 hospitals and a much greater
proportion of total penicillin consumption in Scandinavian hospitals (Figure
5).13,15
In contrast, beta-lactamase inhibitor combinations (such as
amoxicillin/clavulanate) comprised a small component of total penicillin
consumption in Scandinavian hospitals, a larger proportion of total penicillin
consumption in ADHB and Australian hospitals and a very large proportion of
total penicillin consumption in France, Belgium, and
Greece.17
Figure 5. Proportional consumption of different
penicillin classes by adult inpatients in ADHB hospitals in 2009; Australian
hospitals in 2009;16 Swedish hospitals in
2008;13 Norwegian hospitals in
2008;15 and in French, Belgian, and Greek
hospitals in 200217
 Note: Beta-lactamase sensitive
penicillins include benzyl penicillin and phenoxymethylpenicillin;
beta-lactamase resistant penicillins include flucloxacillin and dicloxacillin;
extended spectrum penicillins include amoxicillin and ticarcillin;
beta-lactamase inhibitor combinations include amoxicillin/clavulanate and
ticarcillin/clavulanate.
A number of antimicrobial classes are regarded as
“last-line” because there are few, if any, convenient alternative
agents that can be used in the event of emergence of resistance to these
classes. The ADHB hospitals have a relatively restrictive antimicrobial
stewardship policy that is intended to constrain the consumption of
fluoroquinolones (predominantly ciprofloxacin and norfloxacin), third and fourth
generation cephalosporins (predominantly ceftriaxone and cefepime), carbapenems
(predominantly meropenem and ertapenem), glycopeptides (predominantly
vancomycin) and some other agents.
Figure 6 shows that the level of consumption of these agents
by adult inpatients in ADHB hospitals is less than that in hospitals in
Australia16 and generally comparable with that
in hospitals in Sweden and Denmark.13,14
The level of consumption of these “last-line”
agents is of course determined, to some degree, by the prevalence of infection
with organisms such as methicillin-resistant Staphylococcus aureus
(MRSA) and ESBL-producing Escherichia coli and Klebsiella
pneumoniae that are resistant to most or all “first-line”
antimicrobial agents.
Fortunately, the prevalence of infection with these
multiresistant organisms is relatively low in inpatients in ADHB hospitals. For
example, during 2009, 12% of blood culture isolates of S. aureus in
ADHB hospitals were MRSA, 4.1% of E. coli and 16.4% of K.
pneumoniae isolated from blood cultures were ESBL positive, and in recent
years disease due to vancomycin resistant enterococci has been extremely
rare.18
As the prevalence of infection with these multiresistant
organisms rises we can expect that the level of consumption of these
“last-line” antimicrobial agents will rise—hastening the
emergence of pan-resistant organisms that are essentially untreatable.
Figure 6. Antimicrobial consumption (DDD/100
inpatient days) for fluoroquinolones, third or fourth generation cephalosporins,
carbapenems and glycopeptides by adult inpatients in ADHB hospitals during 2008
compared with consumption of agents within these antibiotic classes by adult
inpatients in hospitals in Australia, Sweden and Denmark during
200813,14,16
 Note: Data was not available on the
level of consumption of third of fourth generation cephalosporins in Sweden
during 2008.
We found that the total level of consumption of
antimicrobials, and of restricted antimicrobial classes, was considerably higher
in the DCCM, CVICU and the haematology ward than in the rest of the hospital
(Figure 3).
The relatively high total levels of consumption in the DCCM
(182 DDDs/100 inpatient days in 2009) and the CVICU (108 DDDs/100 inpatient days
in 2009) were similar to those in 48 ICUs in Sweden in 2009 (median=135 DDDs/100
inpatient days, range=68-270)13 and 24 ICUs in
Australia in 2009 (median=158 DDDs/100 inpatient days,
range=118–222).16
The total consumption of antimicrobials by inpatients in the
haematology ward in 2009 (152 DDDs/100 inpatient days) was less than half that
of the bone marrow transplant unit of the University Hospital in Zurich in
2006.19
This audit has provided a comprehensive overview of the
level of consumption of parenteral and oral antimicrobials by adult inpatients
at Auckland City Hospital in recent years. To the best of our knowledge this is
the first such audit of antimicrobial consumption in a New Zealand hospital.
To ensure comparability of our results with other reports we
followed recently published guidelines on the measurement of the consumption of
antimicrobials.19,20 Because the effective
daily antimicrobial dose in paediatric patients may be very much less than the
DDD, which is a consensus effective adult dose, and because there is a paucity
of published data on inpatient consumption of antimicrobials by paediatric
patients, we confined our analyses to antimicrobial consumption by adult
inpatients.
Our results demonstrate that the current ADHB antimicrobial
stewardship policy is, by and large, achieving its goal of constraining
antimicrobial use in the expectation that this will slow the spread of
antimicrobial resistance and prolong the utility of these essential
medicines.21
Other potential benefits of a prudent antimicrobial
stewardship policy include reducing the incidence of adverse events, such as
allergic reactions and Clostridium difficile colitis, that are a
consequence of antimicrobial therapy, cost minimisation and limitation of
environmental pollution by antimicrobials present in sewerage and wastewater
discharged from the hospital.22 The audit has
identified the potential for changes in the consumption of antimicrobial agents
in the ADHB hospitals that might contribute to slowing the emergence of
antimicrobial resistance in our community.
Such changes include reducing the use of broad spectrum
antimicrobials (such as amoxicillin/clavulanate) and increasing the use of
narrow spectrum antimicrobial agents (such as phenoxymethylpenicillin). We hope
that our results help to encourage consistent, prudent use of antimicrobial
agents by hospital-based clinicians at ADHB and throughout New Zealand.
Competing interests: None.
Author information: Rob Ticehurst,
Medicines Information Manager, Pharmacy; Mark Thomas, Infectious Disease
Physician, Infectious Diseases Department; Auckland City Hospital, Auckland
Acknowledgements: We thank Kathryn Reeves
(of the Information Management and Technical Services Department of the ADHB)
who provided information on numbers of admissions and inpatient occupied bed
days; Malini Subramoney (Pharmacist, ADHB) who provided assistance with data
analyses; and Val Grey (Medical Illustrator) who provided assistance with Figure
3.
Correspondence: Mark Thomas, Infectious
Diseases Department, Auckland City Hospital, Private Bag 92 024, Auckland 1142,
New Zealand. Fax: +64 (0)9 3074940; email: mthomas@adhb.govt.nz
References:
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