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PubMed1995

Mupirocin resistance: clinical and molecular epidemiology.

The antistaphylococcal activity of topical mupirocin has made it an attractive agent for the treatment of asymptomatic colonization with Staphylococcus aureus. Increasing use has been associated with the emergence of mupirocin resistance in staphyloccoci, and failure of therapy has been associated with the isolation of strains exhibiting high-level resistance (MIC > 500 micrograms/mL). Fortunately, low-level mupirocin resistance (MIC < 100 micrograms/mL) occurs most commonly. Because a novel gene encoding for mupirocin resistance resides in both low-level and high-level resistant strains, the emergence of low-level mupirocin resistance may not be as epidemiologically insignificant as previously thought.

Bacterial Typing Techniques↗
PubMed1986

Elimination of nasal carriage of Staphylococcus aureus with mupirocin ('pseudomonic acid')--a controlled trial.

In a blind controlled trial 2% mupirocin ointment was applied four times a day for five days to the anterior nares of 32 healthy volunteers who were followed-up for at least five weeks. Mupirocin eliminated the persistent carriage of Staphylococcus aureus in all subjects within two days of starting mupirocin. Two weeks after the course S. aureus could not be detected, even in low numbers, in nose swabs from any of the 32 volunteers, and even after five weeks only six had resumed carriage. Of the 14 subjects who ultimately resumed carriage, 57% acquired a different phage type and 29% showed a relapse of colonisation with their pre-treatment strain. There was no evidence of overgrowth with Gram-negative organisms and pre- and post-treatment isolates of S. aureus were sensitive to mupirocin with MICs of 0.06 mg/l or less. There were no side-effects. We suggest that mupirocin may become the topical agent of choice for the elimination of S. aureus from the anterior nares.

Adult↗
PubMed1992

Comparison of the in-vitro activities of the topical antimicrobials azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin against methicillin-resistant Staphylococcus aureus.

The in-vitro activities of the topical agents azelaic acid, nitrofurazone, silver sulphadiazine and mupirocin have been determined against 80 strains of MRSA collected from worldwide sources. MICs were determined by agar dilution (with an inoculum of approximately 5.0 x 10(5) cfu) in Iso-Sensitest agar, and MBCs were measured by replica-plating from MIC plates using velvet pads. The agents tested were uniformly active against MRSA, mupirocin being the most active (MIC50 0.15 mg/L) followed by nitrofurazone (MIC50 19 mg/L), silver sulphadiazine (MIC50 85 mg/L) and azelaic acid (MIC50 850 mg/L). Concentrations of azelaic acid, nitrofurazone and silver sulphadiazine close to the MIC were bactericidal, but mupirocin was only bactericidal at concentrations substantially greater than the MIC. In time-kill experiments, azelaic acid and nitrofurazone were gradually bactericidal, silver sulphadiazine was rapidly bactericidal and mupirocin was not bactericidal. Silver sulphadiazine killed sulphonamide-sensitive and sulphonamide-resistant strains equally rapidly. No resistant mutants were found to azelaic acid, nitrofurazone or silver sulphadiazine in an inoculum of 10(9) cfu, but two strains yielded (frequency: 1.0 x 10(-9)) mutants resistant to mupirocin. Our in-vitro results suggest azelaic acid, nitrofurazone and silver sulphadiazine could be of use for clearing staphylococcal carriage.

Anti-Bacterial Agents↗
PubMed1992

Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus.

Twenty one strains of Staphylococcus aureus, of varying resistance to mupirocin, were examined in order to determine the mechanism of resistance to this antibiotic; six of these strains were mupirocin sensitive (MIC 0.12-1.0 mg/L) nine moderately resistant strains (MIC 8-256 mg/L) and six highly resistant strains (MIC > 2048 mg/L). Mupirocin showed a time-dependent inhibition of the target enzyme, isoleucyl-tRNA synthetase (IRS); incubation of the antibiotic with this enzyme before adding the substrates markedly increased inhibition in sensitive strains. The IRS I50 values (the antibiotic concentrations which cause a 50% decrease in enzyme activity) correlated well with the MIC values for each strain (P < 0.01). The mean I50 value for sensitive strains was 3.3 x 10(-2) mg/L, in moderately resistant strains it was 1.3 x 10(-1) mg/L and in highly resistant strains it was 7.5 mg/L. No degradation of mupirocin could be detected during extended incubation of the antibiotic with cell free extracts from four resistant S. aureus strains. We conclude that the production of a modified IRS enzyme is the major cause of mupirocin resistance in the strains studied.

Cell-Free System↗
PubMed1993

Treatment of familial staphylococcal infection--comparison of mupirocin nasal ointment and chlorhexidine/neomycin (Naseptin) cream in eradication of nasal carriage.

Twenty-six families with recurrent staphylococcal infections were treated with either mupirocin nasal ointment (group M) or chlorhexidine neomycin (Naseptin) cream (group N) to the anterior nares, each combined with chlorhexidine soap for washing and chlorhexidine powder applied to other possible carriage sites. Patients receiving mupirocin following failure with chlorhexidine/neomycin (group M/N) were also treated. Treatment was given for seven days to 99 patients, 32 index (infected) patients and 67 family members. Follow-up swabs were collected by a study nurse 8, 14, 28, and 91 days after starting treatment. The carriage of Staphylococcus aureus in the anterior nares was 67%, in the axillae 22%, in the groin 23%, and perianal 19%. The carriage rates in the index patients was higher than family members, in all sites. The eradication of S. aureus from the nasal carriage site after therapy at 8 days was 95% in group M, 85% in group M/N and 61% in group N. Recolonization during the follow-up period was much less in those treated with mupirocin: 57% of patients in group M and 42% in group M/N were not carriers at 91 days, whereas 89% of patients group N were again colonized. Assessment clinically and in terms of prevention of further infective lesions showed that there was a higher response to mupirocin than to chlorhexidine/neomycin. Mupirocin nasal is a successful therapy for removing nasal carriage of S. aureus and has a prolonged effect on recolonization.

Anti-Infective Agents, Local↗
PubMed1995

A double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of mupirocin calcium ointment for eliminating nasal carriage of Staphylococcus aureus among hospital personnel.

Sixty-eight health care workers were enrolled in a double-blind clinical trial and randomized to receive either mupirocin calcium ointment or placebo, intranasally bid for 5 days. Nasal cultures were taken immediately before starting treatment, 1 and 2 during treatment, at the end of treatment, 3 days later, weekly for 1-5 weeks and then monthly for 2-6 months after treatment. Mupirocin eliminated nasal carriage with Staphylococcus aureus in 58% of subjects within two days and 86.7% subjects by the end of therapy compared to 9.4% subjects at the end of treatment with placebo (P < 0.001). Post-treatment colonization rates of 43%, 56% and 67% were attained after 1 month, 2-4 and 6 months treatment with mupirocin respectively and recolonisation with the same strain of S. aureus that had been isolated before treatment was noted in 32%, 40% and 48%. No resistance to mupirocin developed and the drug was well tolerated. Mupirocin is safe and effective in suppressing nasal carriage of S. aureus.

Administration, Intranasal↗
PubMed1992

Staphylococcus aureus and intra-nasal mupirocin in patients receiving isotretinoin for acne.

Thirty patients commencing isotretinoin for acne were entered into a double-blind, randomized, placebo-controlled trial to investigate the effect of pulsed intra-nasal mupirocin ointment on Staphylococcus aureus colonization and isotretinoin-related side-effects. In both mupirocin and placebo groups there was an increase in isolation of S. aureus throughout the period of treatment with isotretinoin from the anterior nares, facial skin and lips. However, these increases were significantly less in the mupirocin-treated group. A high proportion of all patients suffered inflammatory side-effects of isotretinoin such as cheilitis and nasal vestibulitis, with their maximum severities being recorded 2 months after starting isotretinoin. In spite of the smaller increase in S. aureus colonization in the mupirocin-treated group no difference was demonstrated in either the incidence of specific S. aureus infections (e.g. furunculosis) or the prevalence of isotretinoin-related inflammatory side-effects. Furthermore, no relationship between the presence of S. aureus and the severity of inflammatory side-effects was shown. Streptococcus species were isolated on four separate occasions from four different patients during the study but their pathogenicity was unclear. These findings suggest that although pulsed intra-nasal mupirocin produces a significant reduction in isotretinoin-related staphylococcal colonization, its routine use cannot be justified on the basis of clinical benefit.

Acne Vulgaris↗
PubMed1985

Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use.

Mupirocin (pseudomonic acid A), an antibiotic produced by Pseudomonas fluorescens, showed a high level of activity against staphylococci and streptococci and against certain gram-negative bacteria, including Haemophilus influenzae and Neisseria gonorrhoeae, but was much less active against most gram-negative bacilli an anaerobes. Nearly all clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis, including multiply resistant strains, were susceptible (mupirocin MIC, less than or equal to 0.5 microgram/ml). There was no cross-resistance between mupirocin and clinically available antibiotics, and the selection of resistant variants in vitro occurred at a low frequency. Mupirocin was highly bound (95% bound) to the protein of human serum, and activity was reduced 10- to 20-fold in the presence of human serum. The activity of mupirocin was not greatly influenced by inoculum size but was significantly enhanced in acid medium. In tests of bactericidal activity, MBCs were 8- to 32-fold higher than MICs and the antibiotic demonstrated a slow bactericidal action in time-kill tests, resulting in 90 to 99% killing after 24 h at 37 degrees C.

Anti-Bacterial Agents↗
PubMed1994

Mupirocin resistance among consecutive isolates of oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus at a university hospital.

Mupirocin resistance was determined in consecutive oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus clinical isolates collected over 14 months at a university hospital during 1991 and 1992. Twenty of 86 (23%) oxacillin-resistant and borderline oxacillin-resistant S. aureus isolates were mupirocin resistant; 80% were high-level resistant. Prior mupirocin use was a significant risk factor (relative risk, 6.08; 95% confidence interval, 3.7 to 9.99). Seven of 20 resistant isolates were distinct strains, as determined by pulsed-field gel electrophoresis typing. Two instances of clonal dissemination of a single strain occurred, but several other distinct mupirocin-resistant strains were documented. Mupirocin resistance was unexpectedly common among these isolates.

DNA, Bacterial↗
PubMed2004

New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci.

Major challenges in diagnostic molecular microbiology are to develop a simple assay to distinguish Staphylococcus aureus from the less virulent but clinically important coagulase-negative staphylococci (CoNS) and to simultaneously determine their antibiotic resistance profiles. Multiplex PCR assays have been developed for the detection of methicillin- and mupirocin-resistant S. aureus and CoNS but not for the simultaneous discrimination of S. aureus from CoNS. We designed a new set of Staphylococcus genus-specific primers and developed a novel quadriplex PCR assay targeting the 16S rRNA (Staphylococcus genus specific), nuc (S. aureus species specific), mecA (a determinant of methicillin resistance), and mupA (a determinant of mupirocin resistance) genes to identify most staphylococci, to discriminate S. aureus from CoNS and other bacteria, and to simultaneously detect methicillin and mupirocin resistance. Validation of the assay with 96 ATCC control strains and 323 previously characterized clinical isolates, including methicillin- and mupirocin-sensitive and -resistant S. aureus and CoNS isolates and other bacteria, demonstrated 100% sensitivity, specificity, and accuracy. This assay represents a simple, rapid, accurate, and reliable approach for the detection of methicillin- and mupirocin-resistant staphylococci and offers the hope of preventing their widespread dissemination through early and reliable detection.

Anti-Bacterial Agents↗
PubMed2004

Activity of mupirocin and 14 additional antibiotics against staphylococci isolated from Latin American hospitals: report from the SENTRY antimicrobial surveillance program.

A total of 1,346 Staphylococcus aureus (SA) and 498 coagulase-negative staphylococcal (CoNS) strains isolated from 11 Latin American medical centers between 2000 and 2001 were tested against mupirocin and other antimicrobial agents by reference broth microdilution method as part of the SENTRY Antimicrobial Surveillance Program. Oxacillin resistance (OR) was detected in 38.6% of S. aureus and in 78.1% of CoNS. The overall resistance rate to mupirocin was low among S. aureus (3.1%; MIC > or =8 microd/ml) but significantly higher among ORSA compared to oxacillin-susceptible SA (5.4% versus 1.7%; p <0.001). Mupirocin-resistant S. aureus strains were detected in 9 of 11 centers, with individual center rates varying between 1.8 and 15.7%. Mupirocin resistance rates were high among CoNS (27.5%) and varied widely (10.0 to 48.9%) among the monitored Latin American medical centers. Mupirocin resistance rates appear to be increasing and routine monitoring for potential resistance seems prudent.

Academic Medical Centers↗
PubMed2004

Oxacillin- and mupirocin-resistant Staphylococcus aureus: in vitro activity of silver sulphadiazine and cerium nitrate in hospital strains.

Nasal carriage is an important reservoir of oxacillin-resistant Staphylococcus aureus (ORSA). Mupirocin is a topical drug used to remove S. aureus from nares. However, isolates resistant to mupirocin have been reported all over the world. Silver sulphadiazine (SSD) is a topical agent, which when associated with cerium nitrate (CN), has been shown to be useful in the treatment of burn infections and could be an alternative drug for patient decolonization. Susceptibility to oxacillin in 203 S. aureus isolates was evaluated by the agar diffusion test, while the agar diffusion and agar dilution methods were used for mupirocin. A PCR-multiplex method was performed to detect the mecA and ileS-2 genes. Minimum inhibitory concentration (MICs) to SSD and CN, used alone or in association, were determined by the agar dilution method. One hundred and sixty-three (80.3%) strains were oxacillin-resistant, and 37 (18.2%) were mupirocin resistant. The MIC of SSD alone or in association with CN was 64 microg/mL, while for CN alone was 2048 microg/mL for all isolates. SSD presented anti-staphylococcal activity at concentrations (64 microg/mL) much lower than those commonly used in commercial preparations (10 mg/g) and had good activity against mupirocin-resistant strains, showing that this drug could be used for nasal decolonization in ORSA carries.

Anti-Infective Agents, Local↗
PubMed1986

Mupirocin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Mupirocin (pseudomonic acid A) is a novel topical antibacterial agent which inhibits bacterial protein and RNA synthesis. It has excellent in vitro activity against staphylococci and most streptococci, but has less activity against other Gram-positive and most Gram-negative bacteria. Its rapid systemic metabolism means it will only be used topically which, combined with its novel chemical structure, should make cross-resistance less likely to occur than with other currently available topical antibacterial agents. Mupirocin 2% ointment administered 2 or 3 times daily has shown excellent efficacy in both primary and secondary superficial skin infections, usually with at least 80% of patients being clinically cured or markedly improved, and over 90% eradication of the bacterial pathogen involved. Efficacy in impetigo and, to a somewhat lesser extent, infected wounds has been particularly convincingly demonstrated, while in other secondary skin infections the clinical response seen with mupirocin was often similar to the high success rate of vehicle alone. Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed. The evidence of efficacy against nasal carriage of Staphylococcus aureus, including methicillin-resistant forms, is encouraging and currently work is being undertaken to improve the acceptability of the vehicle for this use. Side effects are limited to local reactions (in less than 3% of patients) and are no more frequent than observed with the vehicle alone. Thus, mupirocin appears to be a useful addition to the agents available for the treatment of superficial primary skin infections, such as impetigo, although its precise place in therapy remains to be established.

Administration, Cutaneous↗
PubMed2000

[The influence of the use of mupirocin nasal ointment on the incidence of endogenous MRSA infections in an intensive care unit].

Nasal carriage of MRSA is a significant risk-factor for the endogenous MRSA infection in immunocompromised patients. MRSA infection in ICU patients is thus mostly endogenous infection. To evaluate the impact of mupirocin use on the incidence of endogenous infection caused by MRSA in an intensive care unit, we prospectively treated all patients in the unit with mupirocin, 3 times daily for 3 days. This routine use of mupirocin led to eradication of nasal MRSA carriage in 81.8% of surveillance cultures and to a significant reduction in the total incidence of MRSA infection among MRSA carrier patients (0 episode in 11 patients) when compared to historical controls prior to the use of mupirocin (3 episodes in 7 patients). Mupirocin nasal ointment was significantly effective to prevent endogenous MRSA infection.

Administration, Intranasal↗
PubMed2002

[Methicillin-resistant Staphylococcus aureus (MRSA) with high resistance to mupirocin in hospitals of the Gdańsk region].

Occurrence of high-level mupirocin resistance in methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from 18 hospitals in Gdańsk area was determined. The study was carried out on 190 MRSA isolated in 1997-2000 from various clinical samples. The strains were tested for high-level mupirocin resistance by 200 micrograms mupirocin disc. The minimum inhibitory concentrations (MIC) for methicillin were estimated by agar dilution. Sensitivity to other antibiotics was determined in disc-diffusion method and to vancomycin in agar dilution method additionally. The strains were typed by set of 10 experimental phages and compared by the method of PCR-RFLP analysis of coagulase gen restriction fragment length polymorphism. There were low frequency of high-level mupirocin resistance in MRSA strains (4.7%) that were found only in 3 hospitals, in 6 patients. All of them were high-resistant also to methicillin and resistant to doxycyclin, gentamycin, erytromycin, klindamycin, ciprofloksacin, rifampicin, resistant or intermediate sensitive to fusidic acid but sensitive to vancomycin, teikoplanin and bacitracin. The origin all of the MRSA strains high-resistant to mupirocin probably was the same, except one strain, because they were belonged to one genetic type and possessed the same phage pattern.

Bacteriophage Typing↗
PubMed2003

[Use of nasal mupirocin for Staphylococcus aureus: effect on nasal carriers and nosocomial infections].

Staphylococcus aureus is the agent of community-acquired and nosocomial infections. Twenty to 35% of the population permanently carries it in the nose and oropharynx, and additional 50%, carries it intermittently. Topical calcium mupirocin is an antibacterial agent against Staphylococcus aureus recommended to eradicate nasal and hand colonization in patients and health care workers. The prevalence of nasal S. aureus was determined in patients undergoing cardiovascular surgery. In addition, the effect of mupirocine on the number of carriers and rate of nosocomial infections was evaluated. An experimental prospective study was undertaken with two groups of patients: one treated with mupirocin (n = 96), and the other without treatment (n = 95). Tests for presence of nasal S. aureus and nosocomial infections were conducted in all patients. A 34% prevalence of S. aureus carriers was found. A decrease of the prevalence was found in both treated (87%) and untreated patients (33%), but in significantly different proportions (p = 0.0002, RR = 0.22, 95%CI = 0.09-0.054). This result demonstrated the effectiveness of a mupirocin treatment program to decrease numbers of nasal carriers. With regard to nosocomial infection, S. aureus prevalence was 3.6%, occurring mostly in control patients (6 of 7). Total nosocomial infection prevalence was 17.3%, evenly distributed in treated and untreated patients. This suggested that mupirocin use did not decrease the number of nosocomial infections.

Administration, Intranasal↗
PubMed2003

[Mupirocin: prophylaxis of hospital-acquired infections due to Staphylococcus aureus and sanitation of hospital environment].

Clinical efficacy of mupirocin ointment (dermatic and nasal) was evaluated in the treatment of oncologic patients with nosocomial infections of the staphylococcal etiology and carriers of S.aureus among the medical personnel. The use of dermatic ointment of mupirocin, a local antibiotic, in the treatment of the inpatients with nosocomial infections of the staphylococcal etiology allowed to lower at least 2.5 times the number of the prescriptions of vancomycin, a systemic antibiotic. The use of mupirocin nasal ointment provided absolute eradication of S.aureus strains in the carriers. Recolonization of the nasal passages with S.aureus in some carriers started only 3 months after the eradication. A 6-month observation of the carriers after the sanitation showed that the recolonization frequency by the end of the observation period amounted to 19%. A prolonged for more than 4 months effect of the treatment with mupirocin was stated in 81% of the cases. The monitoring of S.aureus circulation in the intrahospital environment revealed that its level during that period was 6 times lower than the initial one which was obviously due to the use of mupirocin (dermatic and nasal) for the carrier sanitation and the patient treatment.

Administration, Intranasal↗
PubMedDate not supplied

Decrease in infections with the introduction of mupirocin cream at the peritoneal dialysis catheter exit site.

UNLABELLED: Staphylococcus aureus associated peritonitis and catheter exit site infections (ESI) are an important cause of hospitalization and catheter loss in the patients undergoing chronic peritoneal dialysis (PD). We aimed to determine the potential effectiveness of the application of mupirocin cream at the catheter exit site in preventing exit site infection and peritonitis. METHODS: This prospective historically controlled study was done in a total of 86 patients who entered our PD program from April 1999 to January 2001. They were instructed to apply Mupirocin cream 2% to the exit site daily or on alternate days. The patients were not screened to determine whether they were staphylococcus aureus carriers. One hundred and thirteen patients on PD prior to April 1999 acted as historical controls. Both groups were followed prospectively for a period of 22 months. RESULTS: In the study group application of mupirocin lead to a significant reduction in the incidence rate of both exit site infections overall (0.43 vs. 0.09; p<0.0001) and ESI due staphylococcus aureus (0.14 vs. 0.02; p=0.004) amounting to a relative reduction of 79% and 85% respectively. Although the overall incidence of peritonitis did not change (0.28 vs. 0.26; p=0.7) there was a significant reduction in peritonitis caused by staphylococcus aureus (0.07 vs. 0; p=0.01) Although only one catheter required removal in the mupirocin group as against 5 in the control group, this was not statistically significant. CONCLUSIONS: Mupirocin application at the exit site significantly lowers the incidence of ESI and peritonitis caused by staphylococcus aureus without any significant side effects.

Adult↗