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PubMedDate not supplied

Molecular fingerprinting of mupirocin-resistant methicillin-resistant Staphylococcus aureus from a burn unit.

OBJECTIVES: To characterize mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients in a burn unit by pulsed-field gel electrophoresis and plasmid contents. METHODS: A total of 53 methicillin-resistant S. aureus, consisting of 48 mupirocin-resistant and 5 mupirocin-susceptible MRSA were compared by plasmid content and pulsed-field gel electrophoresis of Sma I digested genomic DNA. RESULTS: Of the 48 mupirocin-resistant isolates, 39 expressed high-level, and 9 expressed low-level mupirocin resistance. Plasmids were detected in all of the 53 isolates; however, only the high-level mupirocin-resistant isolates contained a 38 kb-conjugative plasmid that encoded high-level mupirocin resistance. Pulsed-field gel electrophoresis divided the isolates into four patterns designated types I to IV. Forty-three isolates consisting of 34 high-level, 5 low-level mupirocin-resistant and 4 mupirocin-susceptible isolates defined the type-I pattern. Eight isolates, five high-level and three low-level mupirocin-resistant isolates had the type-II pulsed-field pattern. The type-III and type-IV pulsed-field patterns consisted of a single isolate each. The type-I and type-II pulsed-field patterns were related and only differed by four Sma I bands. CONCLUSIONS: Results of typing the mupirocin-resistant MRSA from the burn unit with pulsed-field gel electrophoresis indicated that closely related MRSA clones previously circulating in the unit had acquired a high-level mupirocin-resistant plasmid, and spread aided by mupirocin use.

Anti-Bacterial Agents↗

PubMed2005

Mupirocin for controlling methicillin-resistant Staphylococcus aureus: lessons from a decade of use at a university hospital.

BACKGROUND: From 1990 to 1995 at Hospital Universitário Clementino Fraga Filho, patients colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA) were treated with mupirocin to eliminate MRSA carriage. In 1995, 65% of MRSA patients at this hospital had mupirocin-resistant isolates. Starting in 1996, mupirocin use was restricted to patients colonized, but not infected, with MRSA. OBJECTIVES: To describe the use of mupirocin for controlling MRSA over a decade and to analyze the molecular epidemiology of mupirocin-resistant MRSA infections at this hospital. SETTING: A 490-bed, tertiary-care university hospital. METHODS: The incidence densities of patients with MRSA and acquisition of mupirocin by the hospital were calculated for the period 1992-2001. S. aureus isolates from 1999-2000 were analyzed by pulsed-field gel electrophoresis. Mupirocin-resistant MRSA isolates from 1994-1995 and 1999-2000 were analyzed for ileS-2 gene background polymorphisms. RESULTS: The incidence density of MRSA patients increased slightly over time, whereas the purchase of mupirocin decreased dramatically. Mupirocin-resistant MRSA infections decreased from 65% in 1994-1995 to 15% in 1999-2000. The MRSA Brazilian clone, detected in 1992, was still highly prevalent. The same ileS-2 encoding plasmid found in 1994-1995 persisted in three identical MRSA isolates from 1999-2000 belonging to the Brazilian clone. CONCLUSIONS: After mupirocin use decreased, the ileS-2 encoding plasmid persisted in only a few Brazilian clone isolates. Our data on mupirocin-resistant MRSA incidence and mupirocin use strongly suggested that restricted use was related to decreased rates of mupirocin resistance at our hospital.

Anti-Bacterial Agents↗

PubMedDate not supplied

Decrease in Staphylococcus aureus exit-site infections and peritonitis in CAPD patients by local application of mupirocin ointment at the catheter exit site.

OBJECTIVE: To evaluate the potential effectiveness of the application of mupirocin ointment at the catheter exit site in preventing exit-site infection and peritonitis caused by Staphylococcus aureus (SA). DESIGN: This prospective, historically controlled study was done on 181 peritoneal dialysis patients treated between 1 November 1996 and 1 November 1997. They were instructed to apply mupirocin at the catheter exit site daily or three times per week at the conclusion of their exit-site care (Study 1). The patients were not screened to determine whether they were SA carriers. The group's historical control was the infection data from the previous year among these patients. A second group of 70 patients, who started using mupirocin within a month after catheter implantation (1996-1997), was compared with a historical group of 118 patients (controls) who were on continuous ambulatory peritoneal dialysis (CAPD) for 1 year after in-patient implantation without mupirocin, (1990-1995) (Study 2). RESULTS: In the group of 181 patients (Study 1), application of mupirocin at the exit site led to a significant reduction in SA exit-site infections--21 versus 3 episodes (0.11 vs 0.01 episodes/patient/year)--and a significant reduction of SA peritonitis--35 episodes in the year preceding mupirocin versus 11 episodes during the year of mupirocin treatment (0.19 vs 0.06 ep/pt/yr). The same results were observed in Study 2: the incidence of SA exit-site infection was significantly lower in the mupirocin-treated group--17 episodes among the 118 nontreated patients versus 4 episodes among 70 patients using mupirocin (0.14 ep/pt/yr vs 0.06 ep/pt/yr, respectively). Similarly there were 20 episodes of SA peritonitis among 118 patients during their first year of CAPD versus 4 episodes in 70 mupirocin-treated patients (0.16 ep/pt/yr vs 0.06 ep/pt/yr, respectively). No adverse effects were observed among the patients treated with mupirocin. Overall peritonitis rates decreased from 0.87 to 0.48 ep/pt/yr (p < 0.01) in Study 1 and from 0.56 to 0.41 ep/pt/yr (p = NS) in Study 2. We observed no differences in the incidence of exit-site infection and peritonitis rates among patients applying mupirocin ointment at the exit site daily, compared to three times per week. CONCLUSIONS: Mupirocin application at the exit site significantly lowers the incidence of SA exit-site infections and peritonitis due to SA infections. Since SA infections are accompanied by significant morbidity and occasional mortality, this treatment may improve long-term survival of patients on CAPD.

Administration, Topical↗

PubMed2003

Survey of high- and low-level mupirocin-resistant strains of methicillin-resistant Staphylococcus aureus in 15 Japanese hospitals.

BACKGROUND: The extent of mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA) in countries using mupirocin only for the eradication of nasal carriage of MRSA is unknown. METHODS: During 1997, 1998, 1999, 2000, and 2001, 1368 strains of MRSA were isolated from 15 general hospitals in the Tohoku area of Japan and tested for susceptibility to mupirocin. RESULTS: The isolation of low-level mupirocin resistance was 0.8% in 1997, 1.1% in 1998, 0.7% in 1999, 4.0% in 2000, and 2.4% in 2001. For the first 3 years it was about 1%. However, the isolation rate of low-level mupirocin resistance in MRSA increased dramatically in 2000. High-level mupirocin resistance was not detected during these years. CONCLUSION: Most patients from whom low-level mupirocin resistant MRSA were found in 2000 and 2001 had previously received mupirocin treatment for eradicating nasal carriage of MRSA, and these strains were isolated from sputum or the pharynx. This result indicates that mupirocin treatment is likely to be one of the causes of mupirocin resistance and, therefore, the development of low-level mupirocin resistance in MRSA isolated from sputum or the pharynx should be considered when using mupirocin in order to improve the control of the spread of MRSA in hospitals.

Anti-Bacterial Agents↗

PubMed2001

Emergence and spread of low-level mupirocin resistance in methicillin-resistant Staphylococcus aureus isolated from a community hospital in Japan.

The objective of this study was to investigate the state of mupirocin resistance in methicillin-resistant Staphylococcus aureus (MRSA) in a community hospital in Japan. Ninety strains of MRSA were isolated from the respiratory tract of 56 patients (group I, Jun 1990-Aug 1996) before introduction of mupirocin in Japan, which were compared with 168 strains from 48 patients (group II, Sept 1996-Jan 1998) and 146 strains from 85 patients (group III, Feb 1999-Dec 1999) isolated after introduction of mupirocin. Comparisons were made by determining the minimum inhibitory concentrations (MIC) against nine antibiotics. Fifty-five MRSA isolates from 27 patients [13 (27.1%) of 48 in group II and 14 (16.5%) of 85 in group III] after introduction of mupirocin showed low-level resistance to mupirocin (MIC, 6.25 to 50 microg/ml) but the remaining isolates were sensitive to mupirocin (MIC < or =3.13 microg/ml). Most patients colonized with low-level mupirocin-resistant MRSA were elderly (> or =65 years of age), on total parenteral nutrition or nasal feeding and had other underlying diseases. The proportion of patients colonized with low-level mupirocin-resistant MRSA following repeated use of mupirocin was higher in patients of group II than those of group III. Molecular typing by pulsed-field gel electrophoresis (PFGE) demonstrated that the pattern of 13 MRSA isolates from 13 patients of group II consisted of three patterns (A, B, C) with predominance of pattern A, while the pattern of 13 MRSA isolates from 13 patients of group III consisted of three patterns (A, C, D) with predominance of patterns A and D. Our results indicated that resistance of MRSA to mupirocin remains at a low level at present in Japan. However, we should be aware of the possible emergence of MRSA highly resistant to mupirocin in the future.

Anti-Bacterial Agents↗

PubMed1997

Intranasal mupirocin for outbreaks of methicillin-resistant Staphylococcus aureus.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of mupirocin are reviewed. Mupirocin is a naturally occurring antibiotic produced by submerged fermentation of Pseudomonas fluorescens. It inhibits bacterial protein synthesis by binding reversibly and specifically to isoleucyl-tRNA synthetase. Organisms resistant to other antimicrobials are not simultaneously resistant to mupirocin. Mupirocin is highly active against Staphylococcus aureus and other staphylococci and streptococci. When mupirocin ointment is applied topically, local concentrations exceed the inhibitory concentrations for staphylococci and remain detectable for up to 72 hours. Placebo-controlled studies demonstrate the ability of mupirocin to eliminate nasal carriage of S. aureus in health care workers. Observational studies suggest that mupirocin is efficacious in treating methicillin-resistant S. aureus (MRSA) outbreaks. Preliminary studies show that mupirocin might have a role in preventing infections in high-risk patients. Although mupirocin seems to be well tolerated, mild to moderate adverse events have been reported, including respiratory problems and effects confined to the nose--erythema, swelling, burning or stinging, pruritus, and dryness. Mupirocin calcium ointment has FDA-approved labeling for the eradication of nasal MRSA colonization in adult patients and health care workers as part of comprehensive infection-control programs to reduce the risk of infection during institutional outbreaks. The recommended dosage is 0.5 g inserted into each nostril twice daily for five days. Intranasal mupirocin ointment appears to be a useful addition to infection-control programs designed to reduce the risk of infection among patients during MRSA outbreaks.

Administration, Intranasal↗

PubMed1989

Mechanism of mupirocin transport into sensitive and resistant bacteria.

Pseudomonic acid A (mupirocin) blocks protein synthesis in bacteria by inhibition of bacterial isoleucyl-tRNA synthetase. [16, 17-3H]mupirocin, isolated from a methionine auxotroph of Pseudomonas fluorescens, was used to study transport of this antibiotic into sensitive and resistant strains of Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. The transport of mupirocin into sensitive bacteria was energy independent and temperature dependent (decreased uptake at lower temperatures), indicating non-carrier-mediated passive diffusion. Uptake was also saturable with time or increasing antibiotic concentration. The saturable intracellular binding site, most likely the target isoleucyl-tRNA synthetase as determined by the amount of bound mupirocin (2,700 to 3,100 molecules per cell), caused concentration of the antibiotic within the cell. E. coli transformed with a plasmid containing ileS overproduced the target enzyme and demonstrated greater accumulation of mupirocin than a strain containing a control plasmid. The concentrations needed to half saturate (Kd) these binding sites in B. subtilis and S. aureus were 35 and 7 nM, respectively. In gram-positive organisms trained for mupirocin resistance, uptake was not saturable with increasing antibiotic concentration, and intra- and extracellular concentrations of drug equilibrated with time. Kinetic analysis of crude isoleucyl-tRNA synthetase from trained and untrained B. subtilis strains revealed differences in apparent Ki for mupirocin (resistant strain SB23T, Ki = 71.1 nM; sensitive strain SB23, Ki = 33.5 nM), while the Km for isoleucine remained unchanged (2.7 to 2.9 microM). A Km of 0.4 micromolar isoleucine and Ki of 24 nM mupirocin was demonstrated for isoleucyl-tRNA synthetase from sensitive S. aureus 730a, while no isoleucyl-tRNA synthetase activity was detected in extracts of resistance-trained S. aureus 3000 even at 40 micromolar isoleucine, suggesting instability of the enzyme. Free isoleucine pools differed between sensitive (0.26 micromolar) and resistance-trained (1.06 micromolar) S. aureus. Our results demonstrate that (i) mupirocin enters cells by passive diffusion, (ii) mupirocin concentrates in sensitive bacteria due to binding to isoleucyl-tRNA synthetase, and (iii) resistance to mupirocin involves restricted access to the binding site of isoleucyl-tRNA synthetase.

Amino Acids↗

PubMed1993

High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases.

Mupirocin resistance in Staphylococcus aureus results from changes in the target enzyme, isoleucyl-tRNA synthetase (IRS). Twelve strains of S. aureus comprising four susceptible (MICs < or = 4 micrograms/ml), four intermediate level-resistant (MICs between 8 and 256 micrograms/ml), and four highly resistant (MICs > or = 512 micrograms/ml) isolates were examined for their IRS content and the presence of a gene known to encode high-level mupirocin resistance. Ion-exchange chromatography of cell extracts showed a single IRS active peak in mupirocin-susceptible strains, with 50% inhibitory concentrations (IC50s) of 0.7 to 3.0 ng of mupirocin per ml. In strains showing intermediate mupirocin resistance, similar single IRS activity peaks were observed, but these were less sensitive to inhibition, and the mupirocin IC50s for them were 19 to 43 ng/ml. Strains that were highly resistant to mupirocin displayed two distinct peaks; one was similar to that found with susceptible strains (IC50, 0.9 to 2.5 ng/ml), but an additional peak with an IC50 of 7,000 to 10,000 ng/ml was also observed. A strain cured of the plasmid encoding high-level mupirocin resistance lacked the resistant IRS peak. Restriction digests, produced by endonuclease NcoI, of total bacterial DNA isolated from the highly resistant strains hybridized with a mupirocin resistance gene probe, whereas DNA isolated from the intermediate level-resistant and susceptible strains did not. These results demonstrate that two different IRS enzymes were present in highly mupirocin-resistant S. aureus strains. In strains expressing intermediate levels of resistance, only a chromosomally encoded IRS which was inhibited less by mupirocin than IRS from fully susceptible strains was detected.

Base Sequence↗

PubMed1999

Perianal candidosis--a comparative study with mupirocin and nystatin.

OBJECTIVE: To assess the efficacy and clinical outcome of 2% mupirocin in a polyethylene glycol base and nystatin cream as treatment regimens in diaper candidosis. DESIGN: A prospective randomized comparative study. METHODS: In vitro. The susceptibility of 20 clinical isolates of Candida albicans to 2% mupirocin, nystatin, and five additional antifungal agents was evaluated using the Nathan agar-well diffusion assay. The minimum inhibitory concentration (MIC) of mupirocin against the Candida species was determined using a tube dilution method. In vivo. Twenty patients (mean age, 12 months; range, 1 month to 4 years) with moderate to severe Monilia diaper dermatitis either had mupirocin ointment or nystatin cream applied to the infected area every 8 h or after every diaper change for a period of 7 days. Microscopic examination of skin scrapings and mycologic and microbiological cultures were performed before treatment and daily for 7 days, and progress was clinically assessed. RESULTS: In vitro. Topical mupirocin produced a greater zone of inhibition than nystatin cream, i.e. a mean of 27.2 mm (SD 1.55) compared with a mean of 17.3 mm (SD 1.08) for nystatin cream. MIC for mupirocin of 512 microg/mL in one case, 256 microg/mL in six cases, 200 microg/mL in 10 cases and 400 microg/mL in three cases were obtained for the 20 clinical isolates. C. albicans also displayed a universal sensitivity to mupirocin and nystatin. In vivo. Eradication of all Candida organisms was achieved within 2-6 days (mean, 2.6 days) in 10 patients receiving topical mupirocin therapy with rapid healing of the excoriated wounds (mean, 4.7 days). Both Gram-positive and Gram-negative bacteria were eradicated from the infected area within the trial period. Ten patients received topical nystatin cream and, in each case, Candida was successfully cleared within 5 days (mean, 2.8 days). Only three wounds were clinically healed within the trial period, however. The remaining seven wounds showed evidence of improved, but ongoing excoriated dermatitis and a heavy growth of polymicrobial organisms. CONCLUSIONS: Both agents eradicated Candida, the major difference being the marked response of the diaper dermatitis to mupirocin. Mupirocin should be applied topically 3-4 times daily or with each diaper change and is an excellent antifungal agent.

Administration, Topical↗

PubMed1999

"Pulse" nasal mupirocin maintenance regimen in patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVE: To determine, among patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who were Staphylococcus aureus nasal carriers, if periodic brief "pulses" of nasal mupirocin calcium ointment 2% after completion of a mupirocin eradication protocol would maintain these patients free of carriage. DESIGN: Noncomparative, nonblinded study with historical controls. SETTING: A county medical center. PATIENTS: Patients in a CAPD program during the period April 1996 to May 1998. METHODS: All patients in the CAPD program had monthly nasal cultures for S. aureus. After informed consent, S. aureus nasal carriers were administered mupirocin to the nares twice a day for 5 days followed by nasal mupirocin twice monthly. Peritonitis and exit-site infection rates were monitored independently by CAPD nursing staff. Patients were monitored monthly for adverse effects of mupirocin and compliance with the maintenance regimen. RESULTS: Twenty-four patients in the CAPD program were enrolled in the study and had a median duration of follow-up of 8.5 months. Fifteen (63%) of the 24 patients remained free of nasal carriage on follow-up cultures. Of the 9 patients with positive nasal cultures during the study, 8 had only one positive culture. There was no significant difference in the mean yearly peritonitis rate or S. aureus peritonitis rate (January 1995-May 1998). However, there was a significant decrease in the mean yearly exit-site infection rates both overall (from 8.8 episodes per 100 patients dialyzed per month in 1995 to 4.0 in 1998; P = .008) and due to S. aureus (from 5.6 in 1995 to 0.9 in 1998; P = .03). Adverse effects of nasal mupirocin were mild overall; 1 patient was removed from the study due to an allergic reaction to mupirocin. CONCLUSIONS: Among CAPD patients who were S. aureus nasal carriers, periodic brief treatment with nasal mupirocin after an initial eradication regimen kept them free of carriage, for the most part, with few adverse effects. The pulse mupirocin regimen offers simplicity and possibly better compliance, as well as minimizing exposure to this agent, thereby possibly reducing the risk of resistance. Further studies are warranted to compare this regimen to other commonly used mupirocin maintenance regimens in dialysis patients.

Administration, Intranasal↗

PubMed2006

Preoperative use of mupirocin for the prevention of healthcare-associated Staphylococcus aureus infections: a cost-effectiveness analysis.

OBJECTIVE: Staphylococcus aureus is the most common cause of healthcare-associated infections. Intranasal mupirocin treatment probably decreases S. aureus infections among colonized surgical patients. Using cost-effectiveness analysis, we evaluated the cost-effectiveness of preoperative use of mupirocin for the prevention of healthcare-associated S. aureus infections. METHODS: Three strategies were compared: (1) screen with nasal culture and give treatment to carriers, (2) give treatment to all patients without screening, and (3) neither screen nor treat. A societal perspective was taken. Adverse outcomes included bloodstream infection, pneumonia, surgical site infection, death due to underlying illness or infection, readmission, and the need for home health care. Data inputs were obtained from an extensive MEDLINE review and from publicly available government data sources. The following base-case data inputs (and ranges) for sensitivity analysis were used: rate of S. aureus carriage, 23.1% (19%-55%); efficacy of mupirocin treatment, 51% (8%-75%); mupirocin treatment cost, 48.36 US Dollars (24.18-57.74 US Dollars); and hospital costs of bloodstream infection, 25,128 US Dollars (6,194-40,211 US Dollars), pneumonia, 18,366 US Dollars (5,574-28,952 US Dollars), and surgical site infection 16,256 US Dollars (5,119-22,553 US Dollars). Widespread use of mupirocin has been associated with high levels of mupirocin resistance; therefore, a broad range of estimates for efficacy was tested in the sensitivity analysis. PATIENTS: The target population included patients undergoing nonemergent surgery requiring postoperative hospitalization. RESULTS: Both the screen-and-treat and treat-all strategies were cost saving, saving 102 US Dollars per patient screened and 88 US Dollars per patient treated, respectively. In 1-way sensitivity analyses, the model was robust with respect to all data inputs except for the efficacy of mupirocin treatment. If the efficacy is less than 16.1%, then the screen-and-treat strategy is cost incurring. A treat-all strategy was more cost saving if the rate of S. aureus carriage was greater than 42.7%, the mupirocin cost was less than 29.87 US Dollars, or nursing compensation was greater than 64.21 US Dollars per hour. CONCLUSION: Administration of mupirocin before surgery is cost saving, primarily because healthcare-associated infections are very expensive. The level of mupirocin efficacy is critical to the cost-effectiveness of this intervention.

Anti-Bacterial Agents↗

PubMed1998

The prevalence of low- and high-level mupirocin resistance in staphylococci from 19 European hospitals.

The topical agent mupirocin plays a crucial role in strategies designed to control outbreaks of methicillin-resistant Staphylococcus aureus. The extent of high- or low-level mupirocin resistance amongst S. aureus from European hospitals is not known. Six hundred and ninety-nine S. aureus and 249 coagulase-negative staphylococci (CNS) derived from blood, hospital-acquired pneumonia or skin and soft tissue infections from 19 European hospitals were tested for susceptibility to mupirocin and oxacillin. Methicillin sensitivity was found in 72% and 32% of S. aureus and CNS, respectively. High-level mupirocin resistance was detected in 1.6% of S. aureus and 5.6% of CNS isolates, while low-level mupirocin resistance was detected in 2.3% of S. aureus and 7.2% of CNS isolates. Amongst S. aureus, methicillin-resistant isolates were twice as likely to have high- or low-level mupirocin resistance. This difference was less pronounced in CNS. No relationship was found between the site of infection and prevalence of mupirocin resistance. High- and low-level mupirocin resistance was detected amongst staphylococci from 10 and 16 of the hospitals studied, respectively. To maintain the relatively low prevalence of mupirocin resistance in Europe amongst both S. aureus and CNS, the prudent use of mupirocin restricted to defined infection control strategies should be emphasized.

Anti-Bacterial Agents↗

PubMed2002

A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters.

BACKGROUND: Central venous catheters are frequently needed for the provision of haemodialysis, but their clinical usefulness is severely limited by infectious complications. The risk of such infections can be reduced by topical application of mupirocin to the exit sites of non-cuffed catheters or by the use of tunnelled, cuffed catheters. Whether mupirocin offers any additional protection against infection in patients with tunnelled, cuffed haemodialysis catheters has not been studied. METHODS: An open-label, randomized controlled trial was performed comparing the effect of thrice-weekly exit site application of mupirocin (mupirocin group) vs no ointment (control group) on infection rates and catheter survival in patients receiving haemodialysis via a newly inserted, tunnelled, cuffed central venous catheter. All patients were followed until catheter removal and were monitored for the development of exit site infections and catheter-associated bacteraemias. RESULTS: Fifty patients were enrolled in the study. Both the mupirocin (n=27) and control (n=23) groups were similar at baseline with respect to demographic characteristics, comorbid illnesses and causes of renal failure. Compared with controls, mupirocin-treated patients experienced significantly fewer catheter-related bacteraemias (7 vs 35%, P<0.01) and a longer time to first bacteraemia (log rank score 8.68, P<0.01). The beneficial effect of mupirocin was entirely attributable to a reduction in staphylococcal infection (log rank 10.69, P=0.001) and was still observed when only patients without prior nasal Staphylococcus aureus carriage were included in the analysis (log rank score 6.33, P=0.01). Median catheter survival was also significantly longer in the mupirocin group (108 vs 31 days, log rank score 5.9, P<0.05). Mupirocin use was not associated with any adverse patient effects or the induction of antimicrobial resistance. CONCLUSIONS: Thrice-weekly application of mupirocin to tunnelled, cuffed haemodialysis catheter exit sites is associated with a marked reduction in line-related sepsis and a prolongation of catheter survival.

Administration, Topical↗

PubMed2001

Genetic analysis of methicillin-resistant Staphylococcus aureus expressing high- and low-level mupirocin resistance.

Clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) expressing high- and low-level mupirocin resistance were studied to determine the genetic location of mupirocin and other resistance determinants. Mupirocin resistance was confirmed by MIC determination with E-test strips. Curing and transfer experiments were used to establish the genetic location of the resistance determinants and the PCR with mupA-specific primers was used to detect the presence of mupA genes. High-level mupirocin-resistant isolates had MICs >1024 mg/L, whereas the low-level resistant isolates had MICs of 32-128 mg/L. The isolates carried plasmids ranging from 2.8 to 38 kb in size. All of them carried 26- and 3.0-kb plasmids, but only the high-level mupirocin-resistant isolates carried a 38-kb plasmid. Curing and transfer experiments revealed that the 26-kb plasmid encoded resistance to cadmium, mercuric chloride, propamidine isethionate and ethidium bromide and the 38-kb plasmid was a conjugative plasmid encoding high-level mupirocin resistance. One isolate, IBN287, carried both plasmid-borne high-level and chromosomal low-level mupirocin resistance. The mupA gene was detected on the 38-kb plasmid DNA but not in the genomic DNA of the low-level mupirocin-resistant isolates. The genomic DNA of strain IBN287 cured of the 38-kb mupirocin resistance plasmid did not contain mupA. The results suggest that different genes encoded low- and high-level mupirocin resistance in these isolates.

Anti-Bacterial Agents↗

PubMed1996

Identification of chromosomal location of mupA gene, encoding low-level mupirocin resistance in staphylococcal isolates.

Low- and high-level mupirocin resistance have been reported in Staphylococcus aureus. The expression of plasmid-encoded mupA is responsible for high-level mupirocin resistance. Low-level mupirocin-resistant strains do not contain plasmid-encoded mupA, and a chromosomal location for this gene has not previously been reported. We examined high- and low-level mupirocin-resistant S. aureus strains to determine if mupA was present on the chromosome of low-level-resistant isolates. Southern blot analysis of DNA from four mupirocin-resistant strains identified mupA in both high- and low-level mupirocin-resistant strains. Low-level mupirocin-resistant strains contained a copy of mupA on the chromosome, while the high-level mupirocin-resistant isolate contained a copy of the gene on the plasmid. PCR amplification of genomic DNA from each mupirocin-resistant strain resulted in a 1.65-kb fragment, the predicted product from the intragenic mupA primers. This is the first report of a chromosomal location for the mupA gene conferring low-level mupirocin resistance.

Anti-Bacterial Agents↗

PubMed2003

The effects of weekly mupirocin application on infections in continuous ambulatory peritoneal dialysis patients.

Application of mupirocin to the nares or catheter exit site and frequency of mupirocin administration in continuous ambulatory peritoneal dialysis (CAPD) patients remain controversial. The objective of our study was to evaluate, using a historical control group, the efficacy on CAPD-related infections of once-weekly application of mupirocin at the catheter exit site. We instructed 18 CAPD patients, who did not initially use prophylactic antibiotic treatment, about once-weekly application of mupirocin ointment to the exit site as part of their exit-site care. We recorded the incidence of catheter-related infections, the causative micro-organisms, and the rate of catheter loss. We observed 17 acute exit-site infections (AESIs: 0.45 episodes/patient-year) before mupirocin treatment and 2 AESIs (0.06 episodes/patient-year) after treatment. The relative rate of AESI reduction was 86%. Before application of mupirocin, 52% of AESIs were attributable to Staphylococcus-aureus; after mupirocin administration, no AESIs were staphylococcal. Peritonitis episodes were also reduced from 21 before mupirocin treatment (0.56 episodes/patient-year), to 9 after mupirocin administration (0.29 episodes/patient-year). The relative rate of peritonitis reduction was 48%. Once-weekly application of mupirocin to the exit site resulted in a reduction in exit-site infections and peritonitis episodes comparable to those obtained with daily application.

Adult↗

PubMed1996

A randomized trial of Staphylococcus aureus prophylaxis in peritoneal dialysis patients: mupirocin calcium ointment 2% applied to the exit site versus cyclic oral rifampin.

The objective of this study was to compare prophylaxis for Staphylococcus aureus infections in peritoneal dialysis patients using 600 mg cyclic oral rifampin for 5 days every 3 months versus mupirocin calcium ointment 2% applied daily to the exit site. The study design was a prospective randomized trial, controlling for S aureus nasal carriage. Eighty-two continuous ambulatory and continuous cyclic peritoneal dialysis patients (54% male, 71 % white, 34% insulin-dependent, mean prestudy time on peritoneal dialysis 1.2 years) were randomly assigned to cyclic rifampin (n = 41 patients) or daily exit site mupirocin prophylaxis (n = 41 patients). Mean follow-up was 1 year. S aureus catheter infection rates were 0.13/yr with mupirocin and 0.15/yr with rifampin (P = NS). Both rates were significantly lower than the center's historical rate (the period between 1983 and 1992) of 0.46/yr prior to the study (P < 0.001). S aureus peritonitis rates were 0.04/yr with mupirocin and 0.02/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.16/yr (P < 0.02). Catheter loss due to S aureus infections was 0.02/yr with mupirocin and 0/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.12/yr (P < 0.001). There were no side effects in patients using mupirocin, but 12% were unable to continue rifampin due to side effects. We conclude that mupirocin ointment at the exit site and cyclic oral rifampin are equally effective in reducing S aureus catheter infections. In addition, rifampin or mupirocin significantly reduced S aureus peritonitis and catheter loss due to S aureus infections. Mupirocin at the exit site provides an excellent alternative prophylaxis for S aureus infections, particularly in patients who cannot tolerate oral rifampin therapy.

Administration, Cutaneous↗

PubMed2002

A comparison of the efficacy and safety of mupirocin cream and cephalexin in the treatment of secondarily infected eczema.

The efficacy and safety of mupirocin calcium cream were compared with those of oral cephalexin in the treatment of secondarily infected eczema. In this multicentre, double-blind, double-dummy study, 159 patients with secondarily infected eczema (suitable for treatment with topical antimicrobials) and a total skin infection rating scale score of 8 or more were randomized to receive either topical mupirocin cream three times daily or oral cephalexin, 250 mg four times daily, for 10 days (intent-to-treat group). Clinical success (per-protocol group), defined in part as a patient with a response of improvement in the skin infection rating scale, was similar in the two groups: 89% for mupirocin (n = 44) and 82% for cephalexin (n = 38) [P = 0.29; 95% confidence interval (-8.4%, 22.5%)]. Bacteriological success (intent-to-treat group), defined as a patient with a response of eradication, improvement or colonization of bacteria at the end of therapy, however, was significantly higher for mupirocin [50% and 28% in the mupirocin (n = 48) and cephalexin (n = 47) groups, respectively; P=0.005]. Mupirocin cream was as well tolerated as cephalexin; 9% and 13% of patients reported adverse events related or possibly related to study medication in the mupirocin and cephalexin groups, respectively. The most common adverse events overall were diarrhoea and nausea. Mupirocin cream applied three times daily is as effective clinically and superior bacteriologically compared with oral cephalexin given four times daily in the treatment of secondarily infected eczema of limited depth and severity. Mupirocin cream is as well tolerated as oral cephalexin, and more patients prefer the topical regimen, which should improve patient compliance.

Administration, Cutaneous↗