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Vancomycin and teicoplanin use in Victorian hospitals

Marion B Robertson
Med J Aust 1999; 171 (3): 127-131.
Published online: 2 August 1999
Research

Vancomycin and teicoplanin use in Victorian hospitals

Marion B Robertson, Jonathan G A Dartnell and Tony M Korman,
on behalf of the Victorian Drug Usage Evaluation Group

MJA 1999; 171: 127-131
See also Ferguson, Grayson et al & Collignon

Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details
- - More articles on Pharmacology


Abstract Objective: To determine patterns of prescribing of glycopeptide antibiotics (vancomycin and teicoplanin) in Victorian hospitals and identify areas for targeted intervention.
Design: A concurrent, observational, multisite evaluation of drug use.
Setting: Thirty-five Victorian hospitals, 1-14 September 1997.
Study population: Patients commencing a glycopeptide antibiotic course.
Main outcome measures: Rate of glycopeptide antibiotic use; indications; duration of use; main hospitals using glycopeptide antibiotics.
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 interventional strategies.


Introduction 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 antimicrobials.3,4

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 Victorian hospitals.8

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 these antibiotics.


Methods 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 concerning:

  • 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 inpatient separations.

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 χ2 test. Data are presented as proportions, medians and interquartile ranges.


Results

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 courses.

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 staphylococci).

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 specialists.

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 diseases clinicians.

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 gentamicin (15%).

The most frequently prescribed concurrent antibiotics were ceftriaxone and cefotaxime (11% of vancomycin courses), gentamicin (11%), ceftazidime (9%), imipenem (7%), ciprofloxacin (6%) and metronidazole (6%).

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 courses).

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 ticarcillin/clavulanate (5%).

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.


Discussion 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 intervention.

  • 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 confirmation.

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 colitis.11

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 intervention.

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 glycopeptide antibiotics.



Acknowledgements
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.


References
  1. 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.
  2. Heath CH, Blackmore TK, Gordon DL. Emerging resistance in Enterococcus spp. Med J Aust 1996; 164: 116-120.
  3. Reduced susceptibility of Staphylococcus aureus to vancomycin -- Japan, 1996. MMWR Morb Mortal Wkly Rep 1997; 46: 624-626.
  4. 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.
  5. Witte W. Medical consequences of antibiotic use in agriculture. Science 1998; 279: 996-997.
  6. Misan GMH, Martin ED, Smith ER, et al. Drug utilisation review in a teaching hospital: experience with vancomycin. Eur J Clin Pharmacol 1990; 39: 457-461.
  7. 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.
  8. 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, 1997.
  9. Vernon G, Thomson W, editors. Directory of hospital pharmacy and pharmaceutical organisations. Melbourne: Society of Hospital Pharmacists of Australia, 1996.
  10. Department of Human Services Annual Report 1996-97. Melbourne: Department of Human Services, Victoria, 1997.
  11. Therapeutic Guidelines: Antibiotic, 10th ed. Melbourne: Therapeutic Guidelines Limited, 1998.
  12. Schiff GD, Rucker D. Computerized prescribing. Building the electronic infrastructure for better medication usage. JAMA 1998; 279: 1024-1029.

(Received 21 Dec 1998, accepted 17 May 1999)


Authors' details 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.
Email: Jonathan.DartnellATnwhcn.org.au






1: Definitions

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*

Hospital
location
Number of
courses † (patients)
Number of
inpatient separations
Courses per
1000 separations

Melbourne52 (51)‡235622.0
Melbourne49 (48)245520.0
Melbourne38 (37)194319.6
Melbourne37 (37)299712.3
Melbourne33 (30)§141623.3
Regional11 (11)14777.4
Melbourne10 (9)53818.6
Melbourne10 (10)14776.7
Melbourne9 (9)10718.4
Melbourne8 (8)10897.3
Melbourne8 (7)13575.9
Melbourne7 (7)42316.5
Regional5 (5)8086.2
Melbourne5 (5)10554.7
Melbourne3 (3)15002.0
Melbourne3 (2)27111.1
Regional3 (3)3748.0
Regional2 (2)§14613.7
Melbourne2 (2)8772.3
Melbourne2 (2)4694.3
Melbourne1 (1)6681.5
Regional1 (1)7251.4
Regional1 (1)§2663.8
Melbourne1 (1)6361.6
Melbourne1 (1)5102.0
Overall*302 (293)2944510.3

*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)
  • indications:
 wound infections33 (18.8%)
pneumonia29 (16.5%)
febrile neutropenia21 (11.9%)
septicaemia12 (6.8%)
intravenous catheter-associated sepsis11 (6.3%)
cellulitis9 (5.1%)
infected prosthesis9 (5.1%)
peritonitis/CAPD8 (4.5%)
meningitis3 (1.7%)
other16 (9.1%)
not recorded25 (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 1Hospital 2Hospital 3

Number of courses494938
Number of patients484837
Courses per 1000 separations*20.820.019.6
Vancomycin used (g)177371280
Median length of stay (days)121816
Courses given in intensive care9 (18%)9 (18%) 17 (45%)
Courses prescribed by medical unit12 (24%)28 (57%)20 (53%)
Indication: prophylaxis
Number of courses (%)28 (57%)15 (31%)15 (39%)
Number (%) as single doses †28 (100%)7 (47%)9 (60%)
Surgery type (number of courses)
  cardiac2476
  vascular241
  other248
Indication: treatment
Number (%) empirical13 (62%)30 (88%) 19 (83%)
Median duration of courses (days)
  empirical3.73.64.8
  specific3.04.511.0
Indications (number of courses)
  pneumonia724
  wound infection436
  febrile neutropenia181
  other92112
 
Hospital 4Hospital 5

Number of courses3332
Number of patients3229
Courses per 1000 separations*12.322.6
Vancomycin used (g)299118
Median length of stay (days)209
Courses given in intensive care6 (18%)9 (28%)
Courses prescribed by
medical unit30 (91%)17 (53%)
Indication: prophylaxis
Number of courses (%)8 (24%) 16 (50%)
Number (%) as single doses †8 (100%)11 (69%)
Surgery type (number of courses)
  cardiac18
  vascular63
  other15
Indication: treatment
Number (%) empirical18 (72%)10 (62%)
Median duration of courses (days)
  empirical5.51.5
  specific3.02.0
Indications (number of courses)
  pneumonia60
  wound infection33
  febrile neutropenia24
  other149

* 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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Received 26 September 2018, accepted 26 September 2018

  • Marion B Robertson


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