Vancomycin and teicoplanin use in Victorian hospitals

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.

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.

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.

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.

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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