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

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.

Administration, Intranasal↗

In vivo transfer of high-level mupirocin resistance from Staphylococcus epidermidis to methicillin-resistant Staphylococcus aureus associated with failure of mupirocin prophylaxis.

OBJECTIVES: We examined the molecular basis of the emergence of mupirocin resistance in a methicillin-resistant Staphylococcus aureus (MRSA) strain colonizing a nursing home resident undergoing mupirocin prophylaxis. PATIENT AND METHODS: A persistent carrier of mupirocin-susceptible MRSA participated in a trial of mupirocin for nasal decolonization among nursing home residents. During prophylaxis a high-level mupirocin-resistant MRSA emerged in the nasal isolates from this patient. S. aureus and coagulase-negative staphylococci were isolated prior to, during and after 14 days of mupirocin treatment. The staphylococcal isolates and their plasmids were examined by molecular genetic methods. RESULTS: All mupirocin-susceptible and -resistant MRSA isolates possessed the same genotype. The patient was also colonized by a single mupirocin-resistant Staphylococcus epidermidis strain. The mupirocin-resistant MRSA and S. epidermidis strains harboured identical plasmids that carried the mupA determinant and genes for conjugative DNA transfer in staphylococci. These plasmids could be transferred in vitro from both clinical isolates to S. aureus RN2677. CONCLUSIONS: The MRSA strain contained a conjugative plasmid expressing mupA that was identical with that found in the S. epidermidis strain which colonized the patient. These findings suggest that transfer of mupA from S. epidermidis to MRSA probably occurred during mupirocin prophylaxis.

Aged↗

Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective?

OBJECTIVE: To determine the efficacy of mupirocin ointment in reducing nasal colonization with mupirocin-susceptible, methicillin-resistant Staphylococcus aureus (MS MRSA) as well as mupirocin-resistant MRSA (MR MRSA). DESIGN: Prospective evaluation in which patients colonized with MRSA were treated twice daily with 2% topical mupirocin ointment for 5 days. SETTING: James H. Quillen Veterans' Affairs Medical Center. PATIENTS: Forty hospitalized patients with two anterior nares cultures positive for MRSA within a 7-day period. METHODS: Treated patients had post-treatment cultures at day 3 and weeks 1, 2, and 4. Isolates underwent mupirocin-susceptibility testing and DNA typing. MRSA clearance and type turnover were assessed for isolates that were mupirocin-susceptible, low-level (LL) MR MRSA and high-level (HL) MR MRSA. RESULTS: Post-treatment nares cultures on day 3 were negative for 78.5%, 80%, and 27.7% of patients with MS MRSA, LL-MR MRSA, and HLMR MRSA, respectively. Sustained culture negativity at 1 to 4 weeks was more common in the MS MRSA group (91%) than in the LL-MR MRSA group (25%) or the HL-MR MRSA group (25%). Positive post-treatment cultures usually showed the same DNA pattern relative to baseline. Plasmid curing of 18 HL-MR MRSA resulted in 15 MS MRSA and 3 LL-MR MRSA. CONCLUSIONS: Mupirocin was effective in eradicating MS MRSA, but strains of MR MRSA often persisted after treatment. This appeared to reflect treatment failure rather than exogenous recolonization. MR MRSA is now more prevalent and it is appropriate to sample MRSA populations for mupirocin susceptibility prior to incorporating mupirocin into infection control programs.

Administration, Topical↗

Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. The Mupirocin Collaborative Study Group.

Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86-0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus.

Administration, Intranasal↗

Routine use of mupirocin at the peritoneal catheter exit site and mupirocin resistance: still low after 7 years.

OBJECTIVE: The purpose of this study (the third in a series of similar studies) is to evaluate the prevalence of Staphylococcus aureus (SA), methicillin-resistant SA (MRSA) and mupirocin-resistant SA (MuRSA) carriers in a peritoneal dialysis centre where patients have been instructed to use prophylactic mupirocin ointment at the catheter exit site over the last 7 years. METHODS: Swabs were taken from catheter exit site, nares, axillae and groin in 147 chronic peritoneal dialysis out-patients between November 2003 and January 2004. Axillae/groin and nasal samples were pooled and cultured in the same medium, whereas exit site swabs were cultured separately. All SA isolated were tested for methicillin and mupirocin resistance using oxacillin screening plates and E-test strips. RESULTS: Sixteen of 147 patients (10.9%) were found to be SA carriers: of these 13 (8.8%) had a positive nasal/axillae/groin culture; two (1.4%) had both nasal/axillae/groin- and exit site-positive culture; and one (0.7%) had only exit site-positive culture. In these 16 SA carriers, we found mupirocin-resistant strains (MuRSA) in four patients (25%) and MRSA in two patients (12.5%). Among the four MuRSA carriers, one had both nasal/axillae/groin- and exit site-positive culture and three had only nasal/axillae/groin-positive culture. Three high-level resistance and one low-level resistance MuRSA carriers were isolated. One MuRSA strain was also methicillin resistant. All MRSA strains were sensitive to vancomycin and rifampicin. CONCLUSION: After 7 years' routine use of prophylactic mupirocin ointment at the catheter exit site in non-selected chronic peritoneal dialysis patients, MuRSA was found in 25% of SA strains isolated or in 2.7% of the patients. Compared with our previous study, 3 years earlier, there is no significant increase in the MuRSA prevalence in peritoneal dialysis patients who routinely apply mupirocin ointment at the catheter exit site.

Adult↗

Low concentrations of mupirocin in the pharynx following intranasal application may contribute to mupirocin resistance in methicillin-resistant Staphylococcus aureus.

We describe a patient with methicillin-resistant Staphylococcus aureus (MRSA) colonizing the pharynx. The MIC of mupirocin was 0.25 microg/ml before treatment and increased after treatment to 8 microg/ml. Using pulsed-field gel electrophoresis, we confirmed that the genotypes of MRSA that colonized the pharynx before and after the use of mupirocin were identical. We measured the delivery of mupirocin to the pharynx in three normal volunteers and two patients. Low concentrations of mupirocin were present in the pharynx in all cases 10 min to 3 days after intranasal application. Our data suggested that low concentrations of the drug in the pharynx after intranasal application of mupirocin ointment might explain the selection of mupirocin resistance in MRSA.

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The effects of once- or thrice-weekly mupirocin application on mupirocin resistance in patients on continuous ambulatory peritoneal dialysis--first 6 months' experience.

In the present study, we prospectively investigated the effects of once- or thrice-weekly prophylactic application of mupirocin to catheter exit sites on Staphylococcus aureus carriage, methicillin and mupirocin resistance, and catheter-related infections in continuous ambulatory peritoneal dialysis (CAPD) patients. We enrolled 36 CAPD patients (men/women: 21/ 15; mean age: 55.1 +/- 1.4 years) in the study. At the start of the study, patients had been on once-weekly mupirocin treatment for 3.1 +/- 2.0 years. They were then randomly assigned to use mupirocin either once weekly (group I; n = 18; men/women: 10/8; age: 55.3 +/- 1.8 years) or thrice weekly (group II; n = 18; men/women: 11/7; age: 55.0 +/- 2.3 years). During the study period, swabs were taken monthly from nares, axillae, the inguinal area, and the catheter exit site. We evaluated a total of 806 samples in the first 6 months of the study. The two study groups were similar in terms of age and sex. In group I, 5 isolations of S. aureus in 3 patients came from initial S. aureus carriers. During the first 6 months of the study, only 2 new S. aureus carriers were detected in group I, for a total of 7 isolations. Mupirocin resistance (MuR) was present in only 1 isolate and methicillin resistance (MeR) was not observed. In group II, no S. aureus carriers were present at the initial evaluation, and we encountered only 1 new S. aureus carrier during the first 6 months of the study. During the same period, MuR and MeR were absent in group II. During the 6 months, we observed 1 exit-site infection and 1 peritonitis episode attributable to coagulase-negative staphylococcus (CNS) in group I. In group II, we observed 1 exit-site infection attributable to CNS. During the first 6 months of the study, once- or thrice-weekly application of mupirocin to the catheter exit site has not led to any significant change in S. aureus carriage, MeR and MuR, or catheter-related infection in our CAPD patients.

Anti-Bacterial Agents↗

Nasal mupirocin prevents Staphylococcus aureus exit-site infection during peritoneal dialysis. Mupirocin Study Group.

A total of 1144 patients receiving continuous ambulatory peritoneal dialysis in nine European centers was screened for nasal carriage of Staphylococcus aureus. Two hundred sixty-seven subjects were defined as carriers of S. aureus by having had at least two positive swab results from samples taken on separate occasions, and were randomly allocated to treatment or control groups. Members of each group used a nasal ointment twice daily for 5 consecutive days every 4 wk. The treatment group used calcium mupirocin 2% (Bactroban nasal; SmithKline Beecham, Welwyn Garden City, United Kingdom) and the control group used placebo ointment. Patients were followed-up for a maximum period of 18 months. There were 134 individuals in the mupirocin group, and 133 individuals acted as control subjects. There were no differences in demographic data, cause of renal failure, type of catheter, system used, or method of exit-site care between the groups. Similarly, there were no differences in patient outcome or incidence of adverse events between both groups. Nasal carriage fell to 10% in those subjects who received active treatment and 48% in those who used the placebo ointment. There were 55 exit-site infections in 1236 patient-months in the control group and 33 in 1390 patient-months in the treatment group (not significant). S. aureus caused 14 episodes of exit-site infection in the mupirocin group and 44 in the control group (P = 0.006, mixed effects Poisson regression model). There were no differences in the rate of tunnel infection or peritonitis. There was no evidence of a progressive increase in resistance to mupirocin with time. Regular use of nasal mupirocin in continuous ambulatory peritoneal dialysis patients who are nasal carriers of S. aureus significantly reduces the rate of exit-site infections that occurs because of this organism.

Administration, Intranasal↗

Emergence of mupirocin-resistant Staphylococcus aureus in chronic peritoneal dialysis patients using mupirocin prophylaxis to prevent exit-site infection.

OBJECTIVE: To determine the prevalence of the carriage of Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), and mupirocin-resistant Staphylococcus aureus (MuRSA) in chronic peritoneal dialysis (CPD) patients after 4 years of prophylactic mupirocin application to the exit site, in a peritoneal dialysis unit. METHODS: Three swabs were collected from the nares, axillae/groin, and exit site, respectively, from 149 patients on CPD between May and July 2001. All swabs were cultured on solid selective agar (mannitol salt agar) and in mannitol salt broth. Staphylococcus aureus isolates were tested for methicillin resistance using oxacillin screening plates, and mupirocin resistance using E-test strips. Low-level MuRSA was defined as minimum inhibitory concentration (MIC) of 4 mg/mL or more, and high-level MuRSA as MIC of 256 mg/mL or more. RESULTS: Staphylococcus aureus was isolated from 26 (17%) patients (25 from nares/axilla/groin, and 1 from the exit site). High-level MuRSA was isolated from 4 patients (3% of the total study population; 15% of total SA isolates). No MRSA was detected. One patient with high-level MuRSA had peritonitis due to SA, resulting in treatment failure and catheter loss, soon after the swabs were collected for the study. CONCLUSION: We report the emergence of high-level MuRSA in CPD patients after a 4-year practice of continuous use of mupirocin in a small number of patients in our unit. Our results may have significant implications for the future practice of prophylactic use of mupirocin by CPD patients to prevent exit-site infection.

Adult↗

Co-transfer of plasmids in association with conjugative transfer of mupirocin or mupirocin and penicillin resistance in methicillin-resistant Staphylococcus aureus.

Two distinct strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients in a dermatology ward were also resistant to mupirocin. The mupirocin resistance plasmids from both strains were indistinguishable by EcoRI and HindIII restriction digest analysis, except for the presence of genes apparently mediating penicillinase production in some transconjugants. Conjugative transfer of the plasmid mediating mupirocin resistance from one of these strains to a recipient S. aureus was accompanied in some cases by co-transfer of plasmids mediating resistance to tetracycline or erythromycin; in some instances a plasmid which possessed no apparent resistance markers was also transferred. The second strain demonstrated conjugative transfer of penicillin and mupirocin resistance as well as transfer of a plasmid mediating gentamicin resistance, but transfer of erythromycin resistance was not apparently plasmid-mediated.

Anti-Bacterial Agents↗

Topical mupirocin for eradication of MRSA colonization with mupirocin-resistant strains.

Topical mupirocin was able to interrupt colonization of 52% and 68% of methicillin-resistant Staphylococcus aureus (MRSA)-colonized patients carrying mupirocin-resistant and -sensitive strains, respectively, including 44.4% and 85.7% of those colonized only in the nares. Although a trend to decreased effectiveness was seen for clearing mupirocin-resistant MRSA, this agent can decolonize many patients with resistant strains.

Administration, Topical↗

Development of mupirocin resistance among methicillin-resistant Staphylococcus aureus after widespread use of nasal mupirocin ointment.

All methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from colonized or infected patients in a 625-bed public teaching hospital during an epidemic, and for 3 years thereafter, underwent susceptibility testing to mupirocin. Mupirocin resistance among MRSA increased markedly over this period (1990, 2.7%; 1991, 8.0%; 1992, 61.5%; 1993, 65%) in association with increased use of mupirocin ointment as an adjunct to infection control measures.

Administration, Intranasal↗

Prophylactic mupirocin could reduce orthopedic wound infections. 1,044 patients treated with mupirocin compared with 1,260 historical controls.

We analyzed the effect of perioperative elimination of nasal carriage of Staphylococcus aureus using mupirocin nasal ointment on the reduction of the postoperative wound infection rate in orthopedics. In an unblinded intervention trial, we compared 1,044 patients treated with mupirocin (intervention group) with 1,260 historical controls (control group). From each group a random sample of 50 patients was taken. Risk factors were analyzed in these random samples and we found it unlikely that different distributions of risk factors might have influenced the results. The wound infection rates were 14/1,044 in the intervention group and 34/1,260 in the control group (p = 0.02). The rates of wound infections caused by S. aureus were subsequently 7/1,044 and 14/1,260 (p = 0.3). On checking the data we found that prophylaxis had unintentionally not been given to 172 patients in the intervention group. Correction of the data gave a comparable total infection rate, but a further reduced infection rate by S. aureus. Our findings suggest that prophylactic treatment with mupirocin in orthopedic surgery can reduce the infection rate.

Administration, Intranasal↗

Failure of mupirocin-resistant staphylococci to inactivate mupirocin.

Isolates from four UK centres, comprising four Staphylococcus aureus strains and one Staphylococcus epidermidis strain with high-level mupirocin resistance, and one strain each of Staphylococcus aureus and Staphylococcus epidermidis with low-level mupirocin resistance, were assessed for intracellular or extracellular enzymatic alteration of the antibiotic. No change was seen in a number of assays, which included comparative disk diffusion, well diffusion and high-pressure liquid chromatography. Other mechanisms of resistance need to be explored in these isolates.

Anti-Bacterial Agents↗

[Detection of mupirocin resistant staphylococci from patients treated with mupirocin].

Susceptibility testing of mupirocin (MUP) was performed by an agar dilution method according to the National Committee for Clinical Laboratory Standard (NCCLS) to detect the MUP resistance. A total of 434 isolates of methicillin-resistant staphylococci were examined and all of 205 isolates of methicillin-resistant Staphylococcus aureus (MRSA) from 43 hospitals nationwide in 1993 were sensitive to MUP. However, MUP resistance emerged among 228 isolates [185 isolates (88 cases) of MRSA and 43 isolates (28 cases) of methicillin-resistant coagulase negative staphylococci (MR-CNS)] from nasal swabs of patients with MUP treatment between Sep 1996 and Feb 2000 in the Nagoya University Hospital. The high-level MUP resistance (MIC > or = 512 micrograms/mL) was isolated from two patients, one isolate of MRSA and four of S. hominis, respectively. Low-level MUP resistance (MIC 8-128 micrograms/mL) was isolated from three patients, 11 isolates of MRSA, one of S. chromogenes and five of S. epidermidis, respectively. The mupA which encodes the MUP resistant isoleucyl-tRNA synthetase (IRS) were investigated by PCR in these MUP resistant isolates. The mupA was detected only in high-level MUP resistant S. hominis, but not detected in high-level MUP resistant MRSA and low-level MUP resistant isolates. We also investigated the characteristics of the patients with MUP resistance. All of MUP resistant staphylococci were isolated after initiation of MUP treatment. Four patients with MUP resistant MRSA and low-level MUP resistant MR-CNS had MRSA infectious disease and MUP resistant strains were successfully eradicated with vancomycin treatment in two patients. MUP high-level resistant S. hominis, has emerged after MUP treatment for eradication of MRSA. Clinical guidelines for the prudent use of MUP should be generally adopted with careful monitoring of emergence of MUP resistance.

Adult↗

Attempts to eradicate methicillin-resistant Staphylococcus aureus from a long-term-care facility with the use of mupirocin ointment.

PURPOSE: To assess the impact of the use of mupirocin ointment on colonization, transmission, and infection with methicillin-resistant Staphylococcus aureus (MRSA) in a long-term-care facility. PATIENTS AND METHODS: All 321 residents of a Veterans Affairs long-term-care facility from June 1990 through June 1991 were studied for MRSA colonization and infection. MRSA-colonized patients received mupirocin ointment to nares in the first 7 months and to nares and wounds in the second 5 months. The effect of mupirocin use on MRSA colonization and infection was monitored. All S. aureus strains isolated were tested for the development of resistance to mupirocin. RESULTS: A total of 65 patients colonized with MRSA received mupirocin ointment. Mupirocin rapidly eliminated MRSA at the sites treated in most patients by the end of 1 week. Weekly maintenance mupirocin was not adequate to prevent recurrences--40% of patients had recurrence of MRSA. Overall, MRSA colonization in the facility, which was 22.7% +/- 1% prior to the use of mupirocin, did not change when mupirocin was used in nares only (22.2% +/- 2.1%), but did decrease to 11.5% +/- 1.8% when mupirocin was used in nares and wounds. Although colonization decreased, roommate-to-roommate transmission and MRSA infection rates, low to begin with, did not change when mupirocin was used. Mupirocin-resistant MRSA strains were isolated in 10.8% of patients. CONCLUSIONS: Mupirocin ointment is effective at decreasing colonization with MRSA. However, constant surveillance was required to identify patients colonized at admission or experiencing recurrence of MRSA during maintenance treatment. Long-term use of mupirocin selected for mupirocin-resistant MRSA strains. Mupirocin should be saved for use in outbreak situations, and not used over the long term in facilities with endemic MRSA colonization.

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