Surveillance for mupirocin resistance following introduction of routine peri-operative prophylaxis with nasal mupirocin

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Summary

The authors have previously described the successful use of a five-day peri-operative prophylaxis regimen using nasal mupirocin and topical triclosan (PPNMTT) to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection. The present article describes the results of repeated point-prevalence surveillance for four years to determine whether mupirocin resistance has emerged in surgical units using empirical, short-term, peri-operative prophylaxis with nasal mupirocin. Before starting PPNMTT and every six months thereafter for four years, point-prevalence surveillance was performed for nasal S. aureus carriage in all patients on five orthopaedic surgery wards, one vascular surgery ward and one elderly medicine control ward. S. aureus screening and clinical isolates (surgical patients) were undertaken for low- [minimum inhibitory concentration (MIC) 8–128 mg/L] and high-level (MIC>128 mg/L) mupirocin resistance. All isolates were phage typed to determine whether there was evidence of the spread of clonal mupirocin-resistant strains. Of 593, 139 and 206 nasal screening swabs (taken after the regimen had started) from orthopaedic, vascular and control patients, 28%, 24% and 48% (orthopaedic/vascular surgery vs elderly medicine, P<0.001) yielded S. aureus isolates, respectively, and 12%, 11% and 30% (P<0.001) were MRSA positive, respectively. Of the S. aureus nasal screen isolates from orthopaedic/vascular surgery and control patients, 5% and 4%, respectively, were low-level mupirocin resistant (P>0.1). Of 286 (orthopaedic/vascular surgery) and 68 (elderly medicine) clinical S. aureus isolates obtained after the regimen had started, 7% and 9% (P>0.1), respectively, were low-level mupirocin resistant. No high-level mupirocin-resistant isolates were isolated from mupirocin (orthopaedic/vascular surgery) or elderly medicine control ward patients. There was no trend towards increasing prevalence of low-level mupirocin resistance during the four-year study period. The results of phage typing did not support the clonal spread of resistant strains. Long-term follow-up confirmed the efficacy of PPNMTT in reducing the prevalence of nasal carriage of S. aureus and MRSA in orthopaedic and vascular surgery patients. Despite four years of use of PPNMTT, there was no evidence of sustained emergence or spread of mupirocin resistance.

Introduction

Endemic and epidemic spread of methicillin-resistant Staphylococcus aureus (MRSA) has increased interest in the use of targeted antimicrobial prophylaxis notably in the peri-operative period. The authors recently described the successful use of a five-day peri-operative prophylaxis regimen using nasal mupirocin and topical triclosan (PPNMTT) to prevent MRSA infection in patients undergoing orthopaedic surgery.1 Studies have highlighted the potential use of nasal mupirocin prophylaxis to prevent surgical site infections, notably in patients undergoing cardiothoracic surgery2, 3, 4 and possibly upper gastrointestinal surgery.5 A recent report also claimed efficacy for this approach in orthopaedic surgery.6 However, a placebo-controlled study of nasal mupirocin prophylaxis in patients undergoing orthopaedic prosthetic implant surgery found a reduction in S. aureus nasal carriage but no effect on the incidence of surgical site infections.7

It is important to monitor for emergence of mupirocin resistance, particularly when it is used for prolonged periods.8 Indeed, experience has led to the belief that long-term mupirocin usage is invariably accompanied by the emergence of resistance. However, there is a paucity of long-term data about the emergence of mupirocin resistance in units using short-term mupirocin-based prophylaxis. Therefore, the authors performed repeated point-prevalence surveillance for four years to determine whether mupirocin resistance has emerged in two surgical units using empirical, short-term, peri-operative prophylaxis with nasal mupirocin.

Section snippets

Patients and surveillance periods

From April 1999, patients undergoing orthopaedic surgery involving insertion of metal prostheses and/or fixation in three hospitals within Leeds Teaching Hospitals Trust received peri-operative prophylaxis with nasal mupirocin for five days (i.e. from day −1 to day +4), and a shower or bath with 2% v/v triclosan (Aquasept) on the day of (or night before) surgery (henceforth referred to as PPNMT). Information leaflets were given to staff and patients, and teaching was given to staff. This

Results

Of 593, 139 and 206 nasal screening swabs (taken after PPNMTT was commenced) from orthopaedic, vascular and control patients, 28%, 24% and 48% (orthopaedic/vascular vs control patients, chi-squared P<0.001) yielded S. aureus isolates, respectively, and 12%, 11% and 30% of the screening swabs were MRSA positive, respectively (orthopaedic/vascular vs control patients, chi-squared P<0.001). Of the S. aureus nasal screening isolates from orthopaedic/vascular patients (‘mupirocin-exposed’) and

Discussion

High-level mupirocin resistance results from acquisition of mupA, which encodes a resistant variant of isoleucyl-tRNA synthetase, the target enzyme for mupirocin. There is evidence that mupA may be transferable in vivo from coagulase-negative staphylococci to S. aureus.11 Thus, long-term exposure of skin commensal staphylococci (or S. aureus) to mupirocin, for example during prolonged or repeated topical application to prevent catheter exit site infection, may subsequently lead to high-level

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