Vancomycin and teicoplanin use in Victorian hospitals
Marion B Robertson, Jonathan G A Dartnell and Tony M Korman,
of the Victorian Drug Usage Evaluation Group
MJA 1999; 171: 127-131
See also Ferguson, Grayson et al & Collignon
More articles on Pharmacology
Objective: To determine patterns of prescribing of
glycopeptide antibiotics (vancomycin and teicoplanin) in
Victorian hospitals and identify areas for targeted
Design: A concurrent, observational, multisite
evaluation of drug use.
Setting: Thirty-five Victorian hospitals, 1-14
Study population: Patients commencing a glycopeptide
Main outcome measures: Rate of glycopeptide antibiotic
use; indications; duration of use; main hospitals using
Results: 293 patients (269 adults and 24 neonates)
commenced on 302 glycopeptide antibiotic courses: 296 intravenous
(IV) vancomycin courses and three each of oral vancomycin and
parenteral teicoplanin. The overall rate of use was 10.3 courses per
1000 inpatient separations. Of 271 IV vancomycin courses for adults,
176 (65%) were for treatment -- 120 empirically. The median duration
of treatment courses was 4.7 days (interquartile range, 2.0-8.2
days). A flucloxacillin-resistant organism was confirmed for 44% of
treatment courses. Ninety-five IV vancomycin courses were for
prophylaxis, including for cardiac (54%) and vascular surgery
(21%); 82% of prophylactic courses were administered for less than 24
hours. Of all the glycopeptide antibiotic courses, 69% were
administered at five major metropolitan hospitals.
Conclusions: Glycopeptide antibiotic use in Victoria is
concentrated in the major metropolitan hospitals. Prolonged
durations of vancomycin therapy, including for surgical
prophylaxis and empirical therapy not subsequently confirmed by
microbiology findings, would be suitable targets for
The emergence of resistant strains of Staphylococcus aureus
and coagulase-negative staphylococci has resulted in
increased use of the glycopeptide antibiotics vancomycin and
teicoplanin.1 These antibiotics are the
only effective treatments for infections with these pathogens, but
the emergence of vancomycin-resistant enterococci (VRE) threatens
their utility.1,2 VRE can cause serious
life-threatening infections, and can transfer their resistance in
vitro to other pathogens, such as Staphylococcus, rendering
the bacteria resistant to currently available
The emergence of VRE has been linked to both overuse and inappropriate
use of antibiotics such as vancomycin, teicoplanin and
extended-spectrum cephalosporins.2,4 There is also a strong
relationship with the use of glycopeptide antibiotics in
animals.5 Australian studies have
reported inappropriate use of vancomycin ranging from 42% to 65% in
individual hospitals.6,7 Responding to these
concerns, consensus guidelines have been disseminated to all
The aim of this study was to examine patterns of prescribing
vancomycin and teicoplanin in Victorian hospitals in order to
identify potential areas for targeted intervention to improve use of
This study was conducted by the Victorian Drug Usage Evaluation
Group, a multidisciplinary group that aims to promote and improve
coordination of drug use evaluation activities as a means to improve
drug use. All Victorian public and private hospital pharmacy
departments listed in the Society of Hospital Pharmacists of
Australia directory9 were invited to
participate. All patients at participating hospitals who commenced
a course (Box 1) of oral or intravenous (IV) vancomycin or teicoplanin
between 1-14 September 1997 inclusive were enrolled.
Pharmacists at each hospital collected data
- demographic details,
- the indication for antibiotic therapy as determined from the
medical record or by consultation with the prescriber,
- site and source of infection,
- beta-lactam hypersensitivity, and past history of
methicillin-resistant S. aureus (MRSA) or
methicillin-resistant S. epidermidis (MRSE),
- microbiology results of specimens taken up to seven days before or
concurrent with vancomycin or teicoplanin therapy,
- administration of antibiotics before, during and immediately
after vancomycin or teicoplanin therapy, and
- specialist consultation and advice.
Prescription data were collected until the end of the course, until
the day of discharge or death, or until 28 September 1997.
Each hospital provided details of the number of inpatient
separations between 1-14 September 1997. This was used to estimate
the number of glycopeptide antibiotic courses commenced per 1000
Data were evaluated by the Mann-Whitney rank sum test of the
equivalence of medians of samples not drawn from a normally
distributed population. Proportions were compared using the
test. Data are presented as proportions, medians and interquartile
Hospitals: Thirty-five hospitals participated in
the study: 33 of 58 public and two of 14 private hospitals invited to
participate. Twenty hospitals were in the Melbourne metropolitan
area and 15 in regional areas.
Patients: In the study period, 293 patients (mean
age, 54 years; range, 0-90 years; 112 females) commenced a course of
vancomycin or teicoplanin. The 293 patients received 302 courses of
glycopeptide antibiotics -- three teicoplanin, three oral
vancomycin, and 296 intravenous vancomycin (Box 2).
Five of Melbourne's six major metropolitan hospitals participated
and administered 209 (69%) of the 302 courses. Twenty hospitals
enrolled between one and 11 patients and contributed the remaining 93
Glycopeptide antibiotic use in neonates: Four
hospitals enrolled 24 neonates who were prescribed 25 courses of IV
vancomycin, with a median duration of 2.3 days (interquartile range,
2.0-4.6 days). One course was for prophylaxis for abdominal surgery;
the other 24 courses were for empirical treatment. One treatment
course was for respiratory infection and the others were for an
unknown site of infection. Flucloxacillin-resistant organisms
were isolated for six courses (two MRSA, four coagulase-negative
Glycopeptide antibiotic use in adults: Twenty-five
hospitals enrolled 269 adults who commenced 277 glycopeptide
antibiotic courses; 143 (53%) patients were treated by a medical unit
and 126 (47%) by a surgical unit; 73 (27%) of the patients were in an
intensive care unit at some stage during the glycopeptide antibiotic
course. Of the 269 patients, 235 (87%) were discharged, 30 (11%) died,
and 4 (1%) were still in hospital three months after the study.
For 94 courses (34%), specialist consultation for the use of
vancomycin and teicoplanin was noted in the records. More than 80% of
these consultations were with infectious disease/microbiology
There were 263 patients who received 271 courses of IV vancomycin --
176 (65%) for treatment and 95 for prophylaxis (Box 3). Of the 176 IV
vancomycin treatment courses, 120 (68%) were for empirical
treatment and 56 (32%) as specific treatment. Empirical courses were
shorter than specific courses (P < 0.02). Patients being
treated empirically had been in hospital for fewer days before the
course commenced than patients receiving specific treatment
(P < 0.001).
The duration of empirical courses for which a
flucloxacillin-resistant organism was subsequently identified
was significantly greater than that of the unconfirmed courses
(P < 0.05).
Of the other six patients, three received a course of oral vancomycin
for the treatment of confirmed (two cases) or suspected (one case)
Clostridium difficile diarrhoea, and three received IV
teicoplanin for treatment of wound infections (2 patients) or
cellulitis (1 patient), commenced on the advice of infectious
Other antibiotic use in adults: In the seven days
before IV vancomycin treatment courses, the most frequently
prescribed antibiotics were ceftriaxone and cefotaxime (28% of
courses), metronidazole (16%), flucloxacillin (15%), and
The most frequently prescribed concurrent antibiotics were
ceftriaxone and cefotaxime (11% of vancomycin courses), gentamicin
(11%), ceftazidime (9%), imipenem (7%), ciprofloxacin (6%) and
For 14 treatment courses, vancomycin was continued beyond the close
of the study. Immediately following the 162 completed courses (in 162
patients), other antibiotic therapy was commenced for 57 patients
(35%), concurrent antibiotic therapy continued for 35 patients
(22%), and there was no antibiotic therapy for 50 patients (31%).
On-going therapy was not recorded for nine patients (6%), and the
remaining 11 patients (7%) died.
The antibiotics most frequently commenced immediately after
vancomycin were oral flucloxacillin (12 courses), oral fusidic acid
and oral rifampicin (12 courses), and oral ciprofloxacin (eight
For the 95 IV vancomycin prophylaxis courses, other antibiotics were
given concurrently for 46 (48%) courses, most frequently gentamicin
(14% of vancomycin courses), ceftriaxone (14%), cephazolin (6%) and
Comparison of five main vancomycin users: The five
hospitals that used most vancomycin were major metropolitan
university teaching hospitals where use was restricted by protocols
and consultations. Use by number of courses was greatest in Hospital 1
but the total quantity used was less than half that used at Hospital 2
(Box 4). Rate of use was significantly lower in Hospital 4 than in the
other four hospitals. Surgical use of vancomycin predominated in
Hospital 1, while medical use predominated in Hospital 4. Hospitals
2, 3 and 5 had a significantly smaller proportion of single doses for
prophylaxis than Hospitals 1 and 4.
We have examined the pattern of use of vancomycin in a large sample of
Victorian hospitals. We found that use of teicoplanin and oral
vancomycin was low, and that intravenous vancomycin was used
predominantly for empirical treatment or prophylaxis.
Our study is the first to capture a statewide picture of hospital drug
use linked to indication, and we are not aware of any published
comparable multihospital pharmacoepidemiological data.
Based on the number of inpatient separations for Victorian public
hospitals in 1996-97 (about 890 000),10 we reviewed an estimated
82% of public hospital inpatient separations in the two-week study
period. We estimated the overall rate of glycopeptide antibiotic use
to be 10.3 courses per 1000 inpatient separations, which suggests
about 9160 courses are used annually in Victorian public hospitals.
The main limitation of our study was that vancomycin courses were not
individually compared against explicit criteria to determine the
proportion of appropriate use on the basis of indication, dosage and
duration. We chose not to compare against criteria because of the
variety of prescribing restrictions in participating hospitals.
The most frequent indications for empirical IV vancomycin were
febrile neutropenia, pneumonia and wound infections. The
indications for and duration of empirical therapy could be targets
- For pneumonia, IV vancomycin use may be reasonable for
hospital-acquired infections in institutions with a high
prevalence of MRSA.
- For febrile neutropenia, IV vancomycin may be best restricted to
patients with suspected associated IV line sepsis.
- For wound infections, unless there is a high prevalence of MRSA, IV
vancomycin treatment should wait until after microbiological
Oral vancomycin should be restricted to the treatment of
antibiotic-associated colitis due to toxigenic C. difficile
unresponsive to or relapsing after an adequate course of
metronidazole (or bacitracin), or for patients with severe
Clinicians should be encouraged to regularly review the need for
ongoing drug therapy; however, to improve the current situation, we
need effective decision support tools to facilitate timely
attention to important test findings.12 Almost half the treatment
courses were sanctioned or recommended by infectious
diseases/microbiology specialists, who should be familiar with
relevant guidelines for vancomycin use.
Surgical prophylaxis consumed 35% of IV vancomycin courses, with
cardiac and vascular surgery accounting for 75% of prophylactic
courses. The duration of vancomycin prophylaxis was generally
according to recommendations, with 72% of courses given as single
doses and 82% of courses given for less than 24 hours. However, there
was considerable interhospital variation in the duration of
surgical prophylaxis. The implementation of hospital policies on
duration of surgical prophylaxis would be an important target for
Glycopeptide antibiotic use was concentrated in five major
metropolitan teaching hospitals. Although these five hospitals all
had policies in place, vancomycin use varied substantially.
It is of critical importance for patient care and resource management
that there is a conscious effort to preserve the utility of vancomycin
and teicoplanin. This should be founded on good infection control
practice, but there is also a need for all hospitals to implement
effective interventional strategies to improve the use of the
Financial support for the employment of the Project Coordinator was
provided by the Victorian Drug Usage Advisory Committee and the
Victorian Standing Committee on Infection Control. The project was
also reliant on the voluntary work of pharmacists at the
participating hospitals who undertook all the data collection. We
acknowledge the assistance of the other members of the Victorian Drug
Usage Evaluation Group in the planning and execution of the study and
the preparation of this manuscript: Stephanie J Alvarez, Drug
Utilisation Evaluation Pharmacist, Monash Medical Centre; Dr
Jo-anne Brien, Senior Lecturer, Department of Pharmacy Practice,
Monash University (Parkville Campus); Dr Lisa L Ioannides-Demos,
Senior Research Fellow, Department of Epidemiology and
Preventative Medicine, Monash University, and Senior Research
Officer, Victorian Centre for Ambulatory Care Innovation, Alfred
Hospital; Sam Koroneos, Senior Drug Utilisation Pharmacist,
Pharmacy Department, Austin and Repatriation Medical Centre; Anne
Leversha, Senior Lecturer, Monash University, Faculty of Medicine,
and Victorian College of Pharmacy, and Deputy Manager Pharmacy
Services, Latrobe Regional Hospital, Traralgon West; Julie A V Lord,
Senior Drug Information and Clinical Research Pharmacist, St
Vincent's Hospital, Melbourne; Heather J Lyall, Deputy Director of
Pharmacy, Geelong Hospital; Roslyn I McKinnon, Executive Officer,
Victorian Drug Usage Advisory Committee; Associate Professor R
Moulds, Director, Department of Clinical Pharmacology and
Therapeutics, Royal Melbourne Hospital; Susan G Poole, Deputy
Director, Peter MacCallum Cancer Institute; Dr Gail J Ware, Drug
Usage Evaluation Pharmacist, Alfred Hospital.
- Ena J, Dick RW, Jones RN, Wenzel RP. The epidemiology of intravenous
vancomycin usage in a university hospital: a 10 year study. JAMA
1993; 269: 598-602.
Heath CH, Blackmore TK, Gordon DL. Emerging resistance in
Enterococcus spp. Med J Aust 1996; 164: 116-120.
Reduced susceptibility of Staphylococcus aureus to
vancomycin -- Japan, 1996. MMWR Morb Mortal Wkly Rep 1997; 46:
Quale J, Landman D, Atwood E, et al. Experience with a hospital-wide
outbreak of vancomycin-resistant enterococci. Am J Infect
Control 1996; 24: 372-379.
Witte W. Medical consequences of antibiotic use in agriculture.
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teaching hospital: experience with vancomycin. Eur J Clin
Pharmacol 1990; 39: 457-461.
Radford JM, Whitby RM, Looke DFM, Coombes JA. Vancomycin usage
review in the era of vancomycin-resistant enterococci (VRE).
Aust J Hosp Pharm 1997; 27: 1410-1413.
Guidelines for preventing emergence of vancomycin-resistant
enterococci. Melbourne: Victorian Drug Usage Advisory Committee
and the Standing Committee on Infection Control in collaboration
with the Writing Group for the Therapeutic Guidelines: Antibiotic,
Vernon G, Thomson W, editors. Directory of hospital pharmacy and
pharmaceutical organisations. Melbourne: Society of Hospital
Pharmacists of Australia, 1996.
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(Received 21 Dec 1998, accepted 17 May 1999)
Victorian Drug Usage Evaluation Group, Melbourne, VIC.
Marion B Robertson, BPharm, MSc, Project Coordinator.
Royal Melbourne Hospital, Melbourne, VIC.
Jonathan G A Dartnell, BPharm, MPS, Senior Pharmacist,
Department of Clinical Pharmacology and Therapeutics.
Monash Medical Centre, Melbourne, VIC.
Tony M Korman, FRACP, Infectious Diseases Physician.
Reprints will not be available from the authors.
Correspondence: Mr J
G A Dartnell, Department of Clinical Pharmacology and Therapeutics,
c/- Post Office, Royal Melbourne Hospital, VIC 3050.
Course: The administration to a patient of at least one dose of vancomycin or teicoplanin. If a dose was administered more than 24 hours after a previous dose (and the drug was re-prescribed), this was considered a new course. Patients with renal impairment on regimens with dosing intervals longer than 24 hours were considered to have received a continuous course.
Prophylaxis: Antibiotic administration commenced perioperatively to prevent postoperative infection.
Empirical treatment: Antibiotic administration commenced before or without identification of flucloxacillin-resistant bacterial pathogens.
Specific treatment: Antibiotic administration commenced after identification of flucloxacillin-resistant bacterial pathogens.
Duration: Durations of courses were calculated by subtracting the date and time of the first dose from the date and time of the last dose. The duration of a single dose was considered to be 0 hours.
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2: Glycopeptide antibiotic courses commenced in participating hospitals during study period*|
|*Another 9 regional and 1 Melbourne hospital accounted for 2785 inpatient separations but did not use glycopeptide antibiotics during the study period. Intravenous vancomycin except where indicated. Includes 3 courses of teicoplanin. §Includes 1 course of oral vancomycin. Private hospital.
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|3: Intravenous vancomycin courses commenced in adults|
|All treatment courses|
- 176 treatment courses
- median duration, 4.7 days (interquartile range, 2.0-8.2 days)
| ||wound infections||33 (18.8%)|
|febrile neutropenia||21 (11.9%)|
|intravenous catheter-associated sepsis||11 (6.3%)|
|infected prosthesis||9 (5.1%)|
|not recorded||25 (14.2%)|
- Gram-positive bacteria, including Staphylococcus, Streptococcus, Enterococcus and Bacillus species isolated for 113 (64%) courses
- Isolated organism confirmed flucloxacillin-resistant in 78 courses; organism was MRSA in 67 courses
|Empirical treatment courses|
- 120 empirical treatment courses (68% of all treatment courses)
- median duration, 4.4 days (interquartile range, 1.5-8.0 days)
- patients in hospital for median 4.0 days (interquartile range, 1-12 days) before course commenced
- most frequent indications: febrile neutropenia (18%), pneumonia (16%) and wound infections (12%)
- 32 (26%) of patients had history of beta-lactam antibiotic hypersensitivity or a previous infection with MRSA or MRSE. Two patients had a history of severe hypersensitivity that may have necessitated use of vancomycin rather than beta-lactam antibiotics.
- flucloxacillin-resistant organism subsequently identified in 24 (20%) empirical courses
- duration of courses with confirmed resistant organism was 6.9 days (interquartile range, 2.0-13.8 days) compared with 3.9 days (interquartile range, 1.3-6.7 days) for unconfirmed courses (P<0.05)
|Specific treatment courses|
- 56 specific treatment courses (32% of all treatment courses)
- median duration, 6.1 days (interquartile range, 3.0-11.6 days)
- patients in hospital for median 12 days (interquartile range, 4-22 days) before course commenced
|Surgical prophylaxis courses|
- 95 surgical prophylaxis courses
- 68 (72%) single-dose courses, 78 (82%) less than one day, 12 (12%) one to three days, 5 (5%) more than three days
- 12 (13%) were for patients with history of beta-lactam hypersensitivity, including four severe cases, and 5 (5%) were for patients with history of MRSA or MRSE infection
- 51 (54%) used in cardiac surgery; 31 single doses, 12 (24%) lasted more than 36 hours
- 20 (21%) used in vascular surgery; all were single doses
|CAPD=chronic ambulatory peritoneal dialysis. MRSA=methicillin-resistant Staphylococcus aureus. MRSE=methicillin-resistant S. epidermidis.
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4: Comparison of intravenous vancomycin in adults in the major teaching hospitals|
|Hospital 1||Hospital 2||Hospital 3|
|Number of courses||49||49||38|
|Number of patients||48||48||37|
|Courses per 1000 separations*||20.8||20.0||19.6|
|Vancomycin used (g)||177||371||280|
|Median length of stay (days)||12||18||16|
|Courses given in intensive care||9 (18%)||9 (18%)||
|Courses prescribed by medical unit||12 (24%)||28 (57%)||20 (53%)|
|Number of courses (%)||28 (57%)||15 (31%)||15 (39%)|
|Number (%) as single doses ||28 (100%)||7 (47%)||9 (60%)|
|Surgery type (number of courses)|
|Number (%) empirical||13 (62%)||30 (88%)|| 19 (83%)|
|Median duration of courses (days)|
|Indications (number of courses)|
| wound infection||4||3||6|
| febrile neutropenia||1||8||1|
|Hospital 4||Hospital 5|
|Number of courses||33||32|
|Number of patients||32||29|
|Courses per 1000 separations*||12.3||22.6|
|Vancomycin used (g)||299||118|
|Median length of stay (days)||20||9|
|Courses given in intensive care||6 (18%)||9 (28%)|
|Courses prescribed by|
|medical unit||30 (91%)||17 (53%)|
|Number of courses (%)||8 (24%)|| 16 (50%)|
|Number (%) as single doses ||8 (100%)||11 (69%)|
|Surgery type (number of courses)|
|Number (%) empirical||18 (72%)||10 (62%)|
|Median duration of courses (days)|
|Indications (number of courses)|
| wound infection||3||3|
| febrile neutropenia||2||4|
|* Hospital 4 significantly less than Hospitals 1, 2, 3 and 5 (P<0.02). Hospitals 2, 3, and 5 significantly less than Hospital 1 (P<0.01) and Hospital 4 (P<0.1).
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