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PubMed2000

The epidemiology of mupirocin resistance among methicillin-resistant Staphylococcus aureus at a Veterans' Affairs hospital.

OBJECTIVE: To describe the clinical and molecular epidemiology of mupirocin-resistant (MR) and mupirocin-susceptible (MS) methicillin-resistant Staphylococcus aureus (MRSA) at a Veterans' Affairs hospital and to assess risk factors associated with the acquisition of MR MRSA. DESIGN: All clinical MRSA isolates for the period October 1990 through March 1995 underwent susceptibility testing to mupirocin. Mupirocin resistance trends were measured, and MS MRSA and MR MRSA isolates underwent typing by pulsed-field gel electrophoresis (PFGE). A retrospective case-control study was conducted to evaluate risk factors for having MR versus MS MRSA. SETTING: The James H. Quillen Veterans' Affairs Medical Center in Mountain Home, Tennessee, included a 324-bed acute-care hospital, a 120-bed nursing home, and a 525-bed domiciliary. Colonizations and infections with MRSA were endemic, and mupirocin ointment was commonly used. PATIENTS: Inpatients and outpatients at the facility. RESULTS: MS MRSA was recovered from 506 patients and MR MRSA from 126. Among MR MRSA isolates, 58% showed low-level mupirocin resistance (minimum inhibitory concentration [MIC] > or = 4 to 256 microg/mL), and 42% showed high-level mupirocin resistance (MIC > or = 512 microg/mL). A significant increase (P=.002) in the number of high-level MR isolates occurred during the 1993 to 1995 period. A case-control study showed that presence of a decubitus ulcer correlated with high-level resistant isolates (P<.05). The distribution of PFGE patterns did not differ for MR and MS MRSA CONCLUSIONS: Use of mupirocin ointment in a program aimed at managing endemic MRSA infection or colonization resulted in a significant increase in the recovery of high-level MR MRSA isolates. These isolates appeared to emerge from our existing MRSA pool. A case-control study provided few clues concerning patients likely to harbor MR MRSA. We confirmed the position that the extended use of mupirocin ointment should be avoided in settings where MRSA is endemic.

Administration, Topical↗

PubMed2005

Perioperative intranasal mupirocin for the prevention of surgical-site infections: systematic review of the literature and meta-analysis.

OBJECTIVE: To review the evidence evaluating perioperative intranasal mupirocin for the prevention of surgical-site infections according to type of surgical procedure. DESIGN: Systematic review and meta-analysis of published clinical trials. SETTING: Studies included were either randomized clinical trial or prospective trials at a single institution that measured outcomes both before and after an institution-wide intervention (before-after trial). In all studies, intervention and control groups differed only by the use of perioperative intranasal mupirocin in the intervention group. PATIENTS: Patients undergoing general or nongeneral surgery (eg, cardiothoracic surgery, orthopedic surgery, and neurosurgery). MAIN OUTCOME MEASURE: Risk of surgical-site infection following perioperative intranasal mupirocin versus usual care. RESULTS: Three randomized and four before-after trials met the inclusion criteria. No reduction in surgical-site infection rate was seen in randomized general surgery trials (summary estimates: 8.4% in the mupirocin group and 8.1% in the control group; relative risk [RR], 1.04; 95% confidence interval [CI95], 0.81 to 1.33). In nongeneral surgery, the use of mupirocin was associated with a reduction in surgical-site infection in randomized trials (summary estimates: 6.0% in the mupirocin group and 7.6% in the control group; RR, 0.80; CI95, 0.58 to 1.10) and in before-after trials (summary estimates: 1.7% in the mupirocin group and 4.1% in the control group; RR, 0.40; CI95, 0.29 to 0.56). CONCLUSIONS: Perioperative intranasal mupirocin appears to decrease the incidence of surgical-site infection when used as prophylaxis in nongeneral surgery. Given its low risk and low cost, use of perioperative intranasal mupirocin should be considered in these settings.

Administration, Intranasal↗

PubMed2003

Clonal dissemination of mupirocin-resistant staphylococci in Greek hospitals.

OBJECTIVES: To determine the rates of mupirocin resistance in staphylococci during a 4 year period (1999-2002) in Greece. MATERIALS: A total of 1200 Staphylococcus aureus and 2760 coagulase-negative staphylococci (CoNS), consecutively collected from four Greek hospitals located in different geographical areas, were tested for susceptibility to mupirocin using the Etest and a reference agar dilution method. RESULTS: Twenty-four S. aureus (2%) and 532 CoNS (19.2%) were found to be mupirocin-resistant during the study period. High-level mupirocin resistance was detected in 20 S. aureus (1.6%) and in 440 CoNS (15.9%), respectively. No variations in the rates of mupirocin-resistant S. aureus in relation to the year of collection were observed. In contrast, the rate of mupirocin-resistant CoNS increased dramatically from 9% in 1999, to 14% in 2000, 20% in 2001 and reached 33% in 2002. PFGE analysis revealed the presence of one main clone (A) among mupirocin-resistant S. aureus and two main clones (i and a) among Staphylococcus epidermidis isolates. CONCLUSIONS: In Greece, the rate of mupirocin-resistant S. aureus has remained low and steady since 1999. The high rate of mupirocin-resistant CoNS (33%) in 2002 was due mainly to clonal dissemination of epidemic hospital clones.

Anti-Bacterial Agents↗

PubMed2002

Effectiveness of mupirocin and polymyxin B in experimental Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis.

PURPOSE: The purpose of this study was to determine the effectiveness of mupirocin and polymyxin B, alone and in combination, in vitro and in vivo using rabbit models of, and keratitis. METHODS: Rabbit eyes were intrastromally injected with 1,000 colony-forming units (CFUs) of or or 100 CFUs of Rabbits were then treated with 2.7 mg/mL mupirocin, 10,000 U/mL polymyxin B, a mupirocin:polymyxin B combination, or 0.3% ciprofloxacin. Vehicle and untreated controls were also included. Treatment schedules depended on the strain injected. The number of CFUs was determined for all eyes after treatment. RESULTS: The mupirocin:polymyxin B combination was effective for all three genera both in vitro and in vivo. For keratitis, the mupirocin:polymyxin B combination was more effective than either drug alone and significantly reduced the log number of bacteria in the cornea by more than 3 logs compared with the vehicle or untreated controls (p <or= 0.0016). For, the mupirocin:polymyxin B combination treatment significantly reduced the number of CFUs per cornea relative to the individual drugs, vehicle, or untreated controls (p <or= 0.016). For, the mupirocin:polymyxin B combination therapy significantly reduced the number of bacteria in rabbit corneas relative to the individual drugs, vehicle, or untreated groups (p <or= 0.0001). Therapy with the mupirocin:polymyxin B combination was equivalent to ciprofloxacin therapy (p = 0.80). CONCLUSION: The mupirocin:polymyxin B combination was effective in treating experimental, and keratitis.

Animals↗

PubMed1987

Effect of mupirocin on the growth and lifespan of human fibroblasts.

We have examined the effect of the antibiotic mupirocin on the growth and proliferative lifespan of human fibroblasts. Human embryonic lung fibroblasts were grown in Dulbecco's minimal essential medium, containing 10% fetal bovine serum and various concentrations of mupirocin ranging from 0.5-756 micrograms/ml. There is little difference in the rate of exponential growth and the final saturation density reached between control cultures and those grown in 0.5 microgram, 72 micrograms, or 76 micrograms/ml mupirocin. Growth was retarded or inhibited in cultures containing 650-750 micrograms/ml mupirocin. The proliferative lifespan of adult skin fibroblasts was examined in cultures serially subcultivated in medium containing either 7 micrograms/ml or 100 micrograms/ml mupirocin. Cultures incubated in these concentrations of mupirocin were capable of reaching their full proliferative potential. This study shows that the growth and proliferative lifespan of human fibroblasts is unaltered in the presence of at least 100 micrograms/ml mupirocin although growth of human fibroblasts is inhibited by 700 micrograms/ml mupirocin. These observations suggest that long-term use of low but bactericidal concentrations of mupirocin will not impair growth of fibroblasts in healing wounds.

Cell Adhesion↗

PubMed2000

Efficacy of a new cream formulation of mupirocin: comparison with oral and topical agents in experimental skin infections.

A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections. A mouse surgical wound model infected with Staphylococcus aureus or Streptococcus pyogenes was used. Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days. Mupirocin cream was significantly more effective than (P < 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers. Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P < 0.001) than oral erythromycin. It was also similar in efficacy to cephalexin against S. pyogenes but superior against S. aureus (P < 0.01). Mupirocin cream had a similar efficacy to fusidic acid cream against S. aureus but was significantly superior against S. pyogenes (P < 0.01). A hamster impetigo model infected with S. aureus was also used. Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days. On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P < 0.01) and of similar efficacy in the other two studies. Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P < 0.01) to oral erythromycin and cephalexin. Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections.

Administration, Oral↗

PubMed2004

Analysis of mupirocin resistance and fitness in Staphylococcus aureus by molecular genetic and structural modeling techniques.

Chromosomal resistance to mupirocin in clinical isolates of Staphylococcus aureus arises from V(588)F or V(631)F mutations in isoleucyl-tRNA synthetase (IRS). Whether these are the only IRS mutations that confer mupirocin resistance or simply those that survive in the clinic is unknown. Mupirocin-resistant mutants of S. aureus 8325-4 were therefore generated to examine their ileS genotypes and the in vitro and in vivo fitness costs associated with them before and after compensatory evolution. Most spontaneous first-step mupirocin-resistant mutants carried V(588)F or V(631)F mutations in IRS, but a new mutation (G(593)V) was also identified. Second-step mutants carried combinations of previously identified IRS mutations (e.g., V(588)F/V(631)F and G(593)V/V(631)F), but additional combinations also occurred involving novel mutations (R(816)C, H(67)Q, and F(563)L). First-step mupirocin-resistant mutants were not associated with substantial fitness costs, a finding that is consistent with the occurrence of V(588)F or V(631)F mutations in the IRS of clinical strains. Second-step mutants were unfit, but fitness could be restored by subculture in the absence of mupirocin. In most cases, this was the result of compensatory mutations that also suppressed mupirocin resistance (e.g., A(196)V, E(190)K, and E(195)K), despite retention of the original mutations conferring resistance. Structural explanations for mupirocin resistance and loss of fitness were obtained by molecular modeling of mutated IRS enzymes, which provided data on mupirocin binding and interaction with the isoleucyl-AMP reactive intermediate.

Adenosine Monophosphate↗

PubMed1998

Staphylococcus aureus prophylaxis in hemodialysis patients using central venous catheter: effect of mupirocin ointment.

Central venous catheterization is a common technique to establish rapid and temporary access for hemodialysis. However, it is a known risk factor for Staphylococcus aureus infection and bacteremia. Mupirocin is a topical antibiotic with high in vitro anti-staphylococcal activity. A randomized prospective trial was conducted to assess the effectiveness of mupirocin ointment in the prevention of Staphylococcus aureus skin and catheter colonization, and episodes of bacteremia in 136 end-stage renal disease patients. Of these, 67 received skin disinfection at the venous catheter insertion site with povidone iodine (control group), and 69 received the same treatment followed by application of 2% mupirocin ointment at the cannula site after catheter placement and at the end of each dialysis session. Patients were followed until catheter removal and were monitored for the development of Staphylococcus aureus skin/catheter colonization and episodes of bacteremia. Median duration of catheter use was greater in the mupirocin than in the control group (37 versus 20 d, P < 0.01). Patients in the mupirocin group had a significantly lower rate of Staphylococcus aureus isolation from the pericatheter skin (1.76 per 1000 versus 14.27 per 1000 patient-days, P < 0.001) and from the catheter surface (3.17 per 1000 versus 14.27 per 1000 patient-days, P < 0.001). The proportion of patients with Staphylococcus aureus skin infection at the insertion site was lower in the mupirocin group (4.3% versus 23.9%, P = 0.001). Staphylococcus aureus-associated bacteremia was observed in 17 patients (two in the mupirocin group [0.71 episodes per 1000 patient-days] and 15 in the control group [8.92 per 1000 patient-days], P < 0.001). The hazard ratio of developing Staphylococcus aureus bacteremia was 7.2 (95% confidence interval, 1.6 to 31.6) times greater in patients not receiving mupirocin. Mupirocin applied to the insertion site significantly reduces the risk of Staphylococcus aureus skin and catheter colonization, exit-site infection, and Staphylococcus aureus bacteremia in hemodialysis patients.

Adolescent↗

PubMed2004

Mupirocin prophylaxis against nosocomial Staphylococcus aureus infections in nonsurgical patients: a randomized study.

BACKGROUND: Staphylococcus aureus nasal carriage is a major risk factor for nosocomial S. aureus infection. Studies show that intranasal mupirocin can prevent nosocomial surgical site infections. No data are available on the efficacy of mupirocin in nonsurgical patients. OBJECTIVE: To assess the efficacy of mupirocin prophylaxis in preventing nosocomial S. aureus infections in nonsurgical patients. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 3 tertiary care academic hospitals and 1 nonacademic hospital. PATIENTS: 1602 culture-proven S. aureus carriers hospitalized in nonsurgical departments. INTERVENTION: Therapy with mupirocin 2% nasal ointment (n = 793) or placebo ointment (n = 809), twice daily for 5 days, started 1 to 3 days after admission. MEASUREMENTS: Nosocomial S. aureus infections according to defined criteria, in-hospital mortality, duration of hospitalization, and time to nosocomial S. aureus infection. Staphylococcus aureus isolates were genotyped to assess whether infection was caused by endogenous strains. RESULTS: The mupirocin and placebo groups did not statistically differ in the rates of nosocomial S. aureus infections (mupirocin, 2.6%; placebo, 2.8%; risk difference, 0.2 percentage point [95% CI, -1.5 to 1.9 percentage points]), mortality (mupirocin, 3.0%; placebo, 2.8%; risk difference, -0.2 percentage point [CI, -1.9 to 1.5 percentage points]), or duration of hospitalization (median for both, 8 days). However, time to nosocomial S. aureus infection was decreased in the mupirocin group from 12 to 25 days (P > 0.2). A total of 77% of S. aureus nosocomial infections were endogenous. LIMITATIONS: A few infections in both groups may have been missed because investigators assessed a patient for infection only if microbiology culture results were positive for S. aureus. CONCLUSION: Routine culture for S. aureus nasal carriage at admission and subsequent mupirocin application does not provide effective prophylaxis against nosocomial S. aureus infections in nonsurgical patients.

Administration, Intranasal↗

PubMed1987

Mupirocin: a topical antibiotic with a unique structure and mechanism of action.

The chemistry, mechanism of action, antimicrobial activity, pharmacokinetics, clinical efficacy, adverse effects, dosage, and administration of mupirocin are reviewed. Mupirocin, formerly termed pseudomonic acid A, is a topical antibiotic under investigation for the treatment of impetigo and other superficial primary and secondary skin infections. Mupirocin (Bactroban, Beecham Laboratories) is currently formulated as a 2% ointment in a water-miscible polyethylene glycol base. The drug is a unique antimicrobial agent because of its structure and mechanism of action. Mupirocin apparently exerts its antimicrobial activity by reversibly inhibiting isoleucyl-transfer RNA, thereby inhibiting bacterial protein and RNA synthesis. Mupirocin has excellent in vitro activity against staphylococci and most streptococci but less activity against other gram-positive and gram-negative bacteria. The drug will only be used topically because of its rapid and extensive systemic metabolism. Several controlled clinical trials documented that mupirocin was significantly better than the polyethylene glycol vehicle alone or ampicillin and as effective as cloxacillin, dicloxacillin, or erythromycin in producing clinical and bacteriological cures in patients with impetigo and wound infections caused by gram-positive pathogens. Limited studies suggest that mupirocin may also have a role in eradicating nasal carriage of staphylococci. Reported adverse effects are local and may be related to the polyethylene glycol vehicle base. Mupirocin should be useful for treating patients with impetigo and wound infections caused by Staphylococcus aureus. However, additional controlled, comparative clinical studies are needed to identify the role of mupirocin in treating other primary and secondary skin infections and for eliminating nasal carriage of staphylococci.

Administration, Topical↗

PubMed1999

Molecular characterization and transfer among Staphylococcus strains of a plasmid conferring high-level resistance to mupirocin.

In this work, mupirocin resistance was correlated with the presence of plasmids in methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in the Rio de Janeiro Federal University Hospital in Brazil, where topical mupirocin has been used extensively since 1990. Of 19 strains studied, those exhibiting high-level resistance carried a large and relaxable plasmid of about 35 kb. Mupirocin-sensitive derivatives, obtained by growth at 42 C of a strain exhibiting high-level resistance, were devoid of the large plasmid, which was designated pMG1. Mupirocin resistance was transferred to strain RN8411 during overnight filter-matings at low frequencies (7.0 x 10(-9)/donor). The pMG1 plasmid was shown to be responsible for high-level mupirocin resistance in our isolates and to be incompatible with pGO1. Hybridization experiments suggested that mupirocin resistance in pMG1 is due to the presence of the ileS-2 gene. The pMG1 plasmid was successfully and bidirectionally transferred from Staphylococcus aureus to Staphylococcus epidermidis, suggesting that the latter may be a reservoir of this resistance plasmid. No transfer was detected to Staphylococcus haemolyticus. The development of self-transferable high-level mupirocin resistance should be considered when using mupirocin to control the spread of MRSA in hospitals.

Anti-Bacterial Agents↗

PubMed1991

Reduction in the colonization of central venous cannulae by mupirocin.

In an in-vitro simulation of an intravascular cannula enclosed in a fibrin sheath, 0.03 mg1(-1) of mupirocin prevented significant colonization [greater than 15 colony forming units (cfu)] by two clinical isolates of Staphylococcus epidermidis and one each of S. saprophyticus, S. hominis and S. haemolyticus. This suggests that in vivo, where protein binding of mupirocin is 95-97%, 1 mg 1(-1) of mupirocin at the cannula surface would be required to prevent colonization. These results support the findings of our previously published prospective controlled trial, in which mupirocin applied to the insertion sites of 172 internal jugular cannulae reduced the rate of colonization of cannula tips to 5%, compared with 25% for the 186 controls (P less than 0.001). Of the 46 colonized cannula tips from 110 control patients, the same species was isolated from the skin of the insertion site in 67% and from the lumen flush in only 15%. Analysed by patient, mupirocin reduced the proportion of patients with colonized tips from 17% to 3% after 24 h of infection, and from 35 to 10% after 48 h (P = 0.002). The use of agar containing charcoal, as a mupirocin neutralizer, and the incubation of tip-culture plates flooded with the Oxford staphylococcus, gave no evidence of carry over of mupirocin onto cannulae removed from mupirocin-treated patients.

Administration, Topical↗

PubMedDate not supplied

Treatment of chronic rhinosinusitis exacerbations due to methicillin-resistant Staphylococcus aureus with mupirocin irrigations.

INTRODUCTION: Chronic rhinosinusitis (CRS) exacerbations due to methicillin-resistant Staphylococcus aureus (MRSA) are routinely encountered. Treatment often involves intravenous antibiotics that provide only transient benefits. Mupirocin has well-recognized antistaphylococcal activity, and its nasal formulation is approved by the Food and Drug Administration for the eradication of nasal colonization with MRSA. OBJECTIVE: The aim of this study was to describe the use of mupirocin nasal irrigations for the treatment of CRS exacerbations due to MRSA. MATERIALS AND METHODS: Charts of patients who received mupirocin nasal irrigations for MRSA exacerbations of CRS between January 2000 and October 2003 were reviewed. RESULTS: Forty-two MRSA-positive cultures were obtained from 24 patients (mean age, 61 years; range, 38-82 years; 15 women and 6 men). Twenty-eight episodes were treated with mupirocin nasal irrigations and doxycycline; 4 were treated with mupirocin nasal irrigations and trimethoprim-sulfamethoxazole, and 7 episodes were treated with mupirocin nasal irrigations alone. Patients were reevaluated at approximately 4 to 6 weeks. Repeat cultures were not obtained in 12 patients (because of clinical and endoscopic resolution). Adequate follow-up was unavailable for 3 patients, and of the 27 repeat cultures, only 1 grew MRSA. Twelve patients had at least one recurrence, with a mean number of episodes of 1.75 (range, 1-8 episodes). The mean follow-up was 11.8 months (range, 3-27 months). CONCLUSIONS: Mupirocin nasal irrigations may avoid the need for intravenous antibiotics, which often provide temporary benefits and entail greater cost and morbidity. Thus, mupirocin nasal irrigations may provide a relatively simple means for the management of MRSA exacerbations of CRS.

Administration, Intranasal↗

PubMed2002

Emerging elevated mupirocin resistance rates among staphylococcal isolates in the SENTRY Antimicrobial Surveillance Program (2000): correlations of results from disk diffusion, Etest and reference dilution methods.

Staphylococci cause one-third of all serious invasive infections in the SENTRY Antimicrobial Surveillance Program including bacteremias and lower respiratory tract infections. Staphylococci are also commensals of the skin and nasal passages; therefore, topical agents active against these organisms are valuable in preventing infections or transfer of the organisms between patients and/or health care workers. Mupirocin is a potent topical anti-staphylococcal compound, but its effectiveness has been compromised by emerging resistance. In early 2000, the SENTRY Program detected 302 mupirocin-resistant isolates (131 Staphylococcus aureus, and 171 coagulase-negative staphylococci [CoNS]) from the United States (19/25 medical centers), Canada (4/5), Latin America (3/9) and Europe (7/18). One hundred sixty-eight mupirocin-resistant and 59 susceptible isolates were tested further by reference MIC, Etest (AB BIODISK, Solna, Sweden) and disk diffusion (5-microg) methods. Mupirocin resistance rates for blood stream infections varied by geographic area: for S. aureus from 1.9 to 5.6%, and for CoNS from 12.8 to 39.9%. Using elevated mupirocin MIC results, two resistant populations were noted: low-level resistance at 8-128 microg/mL and high-level resistance at > or = 1024 microg/mL. Acceptable correlation was observed between Etest and disk diffusion results (r = 0.84) without serious intermethod interpretive errors. High-level resistant isolates had heavy growth with no visible zone around the disk; low-level resistant isolates produced hazy zones of inhibition, and susceptible strains had clear zones of inhibition at > or = 17 mm. As mupirocin resistance can be plasmid-mediated, the prudent and appropriate use of this topical agent is important to minimize the ongoing development of resistance. Local surveillance for emerging mupirocin resistance appears warranted particularly in the United States and Canada, pragmatically using a disk diffusion test screening. Where more precise data are needed, the Etest is a very accurate method for distinguishing mupirocin low-level from high-level resistance patterns.

Anti-Bacterial Agents↗

PubMed1999

Mupirocin resistance in staphylococci: development and transfer of isoleucyl-tRNA synthetase-mediated resistance in vitro.

Mupirocin resistance could be transferred from highly resistant clinical isolates of Staphylococcus aureus to highly sensitive recipients of Staph. aureus, Staph. epidermidis and Staph. haemolyticus. Transconjugants of the latter two organisms could transfer this resistance into mupirocin-sensitive Staph. aureus. Moderately resistant strains did not transfer this resistance to sensitive recipients, nor did strains with high-level mupirocin resistance developed by serial transfer or habituation. The inhibitory effects of mupirocin on crude isoleucyl-tRNA synthetases (IRS) isolated from mupirocin-sensitive and -resistant strains of Staph. aureus have been determined. Drug concentrations needed to produce 50% inhibition, I50 values, were very low against IRS from a highly sensitive strain, somewhat higher against IRS from moderately resistant strains, much higher against enzyme from strains trained in vitro to high-level resistance, and considerably higher still against IRS extracted from clinical isolates possessing high-level mupirocin resistance and from the transconjugates of such strains resulting from crosses with mupirocin-sensitive strains. It is concluded that high-level resistance in clinical isolates is plasmid-mediated involving a second, mupirocin-resistant IRS whereas in moderately resistant strains, and in strains trained in vitro to high-level resistance, chromosomal mutations are likely to be responsible for decreasing IRS sensitivity.

Anti-Bacterial Agents↗

PubMed2002

Analysis of rILERS, an isoleucyl-tRNA synthetase gene associated with mupirocin production by Pseudomonas fluorescens NCIMB 10586.

Some strains of Pseudomonas fluorescens produce the antibiotic mupirocin, which functions as a competitive inhibitor of isoleucyl-tRNA synthetase (ILERS). Mupirocin-producing strains of P. fluorescens must overcome the inhibitory effects of the antibiotic to avoid self-suicide. However, it is not clear how P. fluorescens protects itself from the toxic effects of mupirocin. In this report, we describe a second gene encoding isoleucyl-tRNA synthetase (rILERS) in P. fluorescens that is associated with the mupirocin biosynthetic gene cluster. Random mutagenesis of the mupirocin-producing strain, P. fluorescens 10586, resulted in a mupirocin-defective mutant disrupted in a region with similarity to ILERS, the target site for mupirocin. The ILERS gene described in the present study was sequenced and shown to be encoded by a 3093 bp ORF, which is 264 bp larger than the ILERS gene previously identified in P. fluorescens 10586. rILERS from P. fluorescens is most closely related to prokaryotic or eukaryotic sources of ILERS that are resistant to mupirocin. Interestingly, the relatedness between rILERS and the ILERS previously described in P. fluorescens 10586 was low (24% similarity), which indicates that P. fluorescens contains two isoforms of isoleucyl-tRNA synthetase.

Amino Acid Sequence↗

PubMed2003

Mupirocin-based decolonization of Staphylococcus aureus carriers in residents of 2 long-term care facilities: a randomized, double-blind, placebo-controlled trial.

Mupirocin has been used in nursing homes to prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA), despite the lack of controlled trials. In this double-blind, randomized study, the efficacy of intranasal mupirocin ointment versus that of placebo in reducing colonization and preventing infection was assessed among persistent carriers of S. aureus. Twice-daily treatment was given for 2 weeks, with a follow-up period of 6 months. Staphylococcal colonization rates were similar between residents at the Ann Arbor Veterans Affairs (VA) Extended Care Center, Michigan (33%), and residents at a community-based long-term care facility in Ann Arbor (36%), although those at the VA Center carried MRSA more often (58% vs. 35%; P=.017). After treatment, mupirocin had eradicated colonization in 93% of residents, whereas 85% of residents who received placebo remained colonized (P<.001). At day 90 after study entry, 61% of the residents in the mupirocin group remained decolonized. Four patients did not respond to mupirocin therapy; 3 of the 4 had mupirocin-resistant S. aureus strains. Thirteen (86%) of 14 residents who became recolonized had the same pretherapy strain; no strain recovered during relapse was resistant to mupirocin. A trend toward reduction in infections was seen with mupirocin treatment.

Aged↗

PubMed1985

In-vitro activity of mupirocin ('pseudomonic acid') against clinical isolates of Staphylococcus aureus.

The in-vitro activity of mupirocin ('pseudomonic acid') was determined against clinical isolates of Staphylococcus aureus with various antibiotic resistance patterns including resistance to methicillin. All 750 isolates were inhibited by 2 mg/l of mupirocin and the MICs for 200 isolates tested on DST agar at pH 7.2 with an inoculum of 10(4) cfu ranged from 0.015 to 0.06 mg/l. Inoculum size, pH, test agar and the method of dissolving mupirocin all influenced the MICs obtained. The minimum concentrations of mupirocin to obtain a 99, and 99.9 and 99.99% kill after 24 h in Iso-Sensitest broth at pH 7.2 were 2-4, 16 and 32 mg/l, respectively. Sterile cultures were obtained when each of five strains were exposed to 1.0 mg/l or more of mupirocin for 120 h. Resistant variants with MICs of up to 4 mg/l were detected at a frequency of approximately 1 X 10(-9) and produced chrome-yellow colonies. Each of five strains could be trained to grow in the presence of 40 mg/l of mupirocin. We conclude that although apparently bacteriostatic, mupirocin has slow bactericidal activity against Staph. aureus and that 2% mupirocin may well be effective for topical treatment of skin infections caused by Staph. aureus and contribute to the control of multiply-resistant strains during hospital outbreaks.

Anti-Bacterial Agents↗