Journal of the New Zealand Medical Association, 15-April-2011, Vol 124 No 1332
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.
All 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.
The 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.
This 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: firstname.lastname@example.org
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