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Biotechnology Letters May 2019Mupirocin is an antibiotic from monocarboxylic acid class used as antibacterial agent against methicillin-resistant Staphylococcus aureus (MRSA) and can be obtained as a... (Review)
Review
Mupirocin is an antibiotic from monocarboxylic acid class used as antibacterial agent against methicillin-resistant Staphylococcus aureus (MRSA) and can be obtained as a mixture of four pseudomonic acids by Pseudomonas fluorescens biosynthesis. Nowadays improving antibiotics occupies an important place in the pharmaceutical industry as more and more resistant microorganisms are developing. Mupirocin is used to control the MRSA outbreaks, for infections of soft tissue or skin and for nasal decolonization. Due to its wide use without prescription, the microorganism's resistance to Mupirocin increased from up to 81%, thus becoming imperative its control or improvement. As the biotechnological production of Mupirocin has not been previously reviewed, in the present paper we summarize some consideration on the biochemical process for the production of pseudomonic acids (submerged fermentation and product recovery). Different strains of Pseudomonas, different culture medium and different conditions for the fermentation were analysed related to the antibiotics yield and the product recovery step is analysed in relation to the final purity. However, many challenges have to be overcome in order to obtain pseudomonic acid new versions with better properties related to antibacterial activity.
Topics: Anti-Bacterial Agents; Carrier State; Drug Resistance, Bacterial; Fermentation; Humans; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Pseudomonas fluorescens; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Technology, Pharmaceutical
PubMed: 30927135
DOI: 10.1007/s10529-019-02670-w -
Clinical Infectious Diseases : An... Sep 2009With increasing pressure to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection, it is possible that there will be increased use of mupirocin for nasal... (Review)
Review
With increasing pressure to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection, it is possible that there will be increased use of mupirocin for nasal decolonization of MRSA. Understanding the mechanisms, clinical significance, and epidemiology of mupirocin resistance is important for predicting how changes in mupirocin use may affect bacterial populations and MRSA control. High-level mupirocin resistance in S. aureus is mediated by a plasmid-encoded mupA gene. This gene can be found on conjugative plasmids that carry multiple resistance determinants for other classes of antimicrobial agents. High-level resistance has been associated with decolonization failure, and increased resistance rates have been associated with increased mupirocin use. Low-level mupirocin resistance is mediated via mutation in the native ileS gene, and the clinical significance of this resistance is unclear. Laboratory tests to detect and distinguish between these types of resistance have been described but are not widely available in the United States. Institutions that are considering the implementation of widespread mupirocin use should consider these resistance issues and develop strategies to monitor the impact of mupirocin use.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Colony Count, Microbial; Conjugation, Genetic; Drug Resistance, Bacterial; Genotype; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mupirocin; Nuclear Proteins; Plasmids; Staphylococcal Infections
PubMed: 19673644
DOI: 10.1086/605495 -
The Journal of Antimicrobial... Oct 2015Mupirocin 2% ointment is used either alone or with skin antiseptics as part of a comprehensive MRSA decolonization strategy. Increased mupirocin use predisposes to... (Meta-Analysis)
Meta-Analysis Review
Mupirocin 2% ointment is used either alone or with skin antiseptics as part of a comprehensive MRSA decolonization strategy. Increased mupirocin use predisposes to mupirocin resistance, which is significantly associated with persistent MRSA carriage. Mupirocin resistance as high as 81% has been reported. There is a strong association between previous mupirocin exposure and both low-level and high-level mupirocin resistance. High-level mupirocin resistance (mupA carriage) is also linked to MDR. Among MRSA isolates, the presence of the qacA and/or qacB gene, encoding resistance to chlorhexidine, ranges from 65% to 91%, which, along with mupirocin resistance, is associated with failed decolonization. This is of significant concern for patient care and infection prevention and control strategies as both these agents are used concurrently for decolonization. Increasing bacterial resistance necessitates the discovery or development of new antimicrobial therapies. These include, for example, polyhexanide, lysostaphin, ethanol, omiganan pentahydrochloride, tea tree oil, probiotics, bacteriophages and honey. However, few of these have been evaluated fully or extensively tested in clinical trials and this is required to in part address the implications of mupirocin resistance.
Topics: Animals; Anti-Bacterial Agents; Chlorhexidine; Disinfectants; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mupirocin; Prevalence; Staphylococcal Infections
PubMed: 26142407
DOI: 10.1093/jac/dkv169 -
Drug and Therapeutics Bulletin Dec 1989
Review
Topics: Administration, Intranasal; Carrier State; Humans; Mupirocin; Nasal Cavity; Ointments; Staphylococcal Infections
PubMed: 2519322
DOI: No ID Found -
International Journal of Antimicrobial... Oct 2023The pathogenicity of Staphylococcus epidermidis is largely attributed to its exceptional ability to form biofilms. Here, we report that mupirocin, an antimicrobial agent...
The pathogenicity of Staphylococcus epidermidis is largely attributed to its exceptional ability to form biofilms. Here, we report that mupirocin, an antimicrobial agent widely used for staphylococcal decolonization and anti-infection, strongly stimulates the biofilm formation of S. epidermidis. Although the polysaccharide intercellular adhesin (PIA) production was unaffected, mupirocin significantly facilitated extracellular DNA (eDNA) release by accelerating autolysis, thereby positively triggering cell surface attachment and intercellular agglomeration during biofilm development. Mechanistically, mupirocin regulated the expression of genes encoding for the autolysin AtlE as well as the programmed cell death system CidA-LrgAB. Critically, through gene knockout, we found out that deletion of atlE, but not cidA or lrgA, abolished the enhancement of biofilm formation and eDNA release in response to mupirocin treatment, indicating that atlE is required for this effect. In Triton X-100 induced autolysis assay, mupirocin treated atlE mutant displayed a slower autolysis rate compared with the wild-type strain and complementary strain. Therefore, we concluded that subinhibitory concentrations of mupirocin enhance the biofilm formation of S. epidermidis in an atlE dependent manner. This induction effect could conceivably be responsible for some of the more unfavourable outcomes of infectious diseases.
Topics: Staphylococcus epidermidis; Mupirocin; Biofilms; Staphylococcus; Virulence; Bacterial Proteins
PubMed: 37385560
DOI: 10.1016/j.ijantimicag.2023.106904 -
International Journal of Dermatology Jan 1992
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Nephrology, Dialysis, Transplantation :... Feb 2010Recently, there have been increasing concerns about the emergence of mupirocin resistance and increased infections due to lowered inhibition of Staphylococcus aureus. We... (Review)
Review
OBJECTIVES
Recently, there have been increasing concerns about the emergence of mupirocin resistance and increased infections due to lowered inhibition of Staphylococcus aureus. We conducted this systemic analysis to find out whether the application of mupirocin was effective for the prevention of exit-site infection (ESI) and peritonitis in patients undergoing peritoneal dialysis (PD).
METHODS
Recruited studies met the following criteria: they were randomized controlled trials or historical cohort studies; subjects consisted of adults (age, >or= 18 years) undergoing PD; mupirocin treatment was administered to the therapy group and placebo or no treatment was administered to the control group. The primary extracted data were the difference in the episodes of ESI and peritonitis S. aureus or other organisms among treatment and control groups. Results. Fourteen studies described in 13 articles and a total of 1,233 patients versus 1,217 controls were included in the analysis. Of the 13 articles, 6 were newly published articles that had not been analysed previously and 3 were randomized controlled trials. The application of mupirocin decreased the risk by 72% [95% confidence interval (CI): 0.60-0.81] in ESI and by 70% (95% CI 0.52-0.81) in peritonitis due to S. aureus among all patients undergoing PD. Treatment of mupirocin reduced the risks of ESI and peritonitis due to all organisms by 57% (95% CI: 0.46-0.66) and 41% (95% CI: 0.24-0.54), respectively. Based on the six newly published articles, the reduced risk rate for mupirocin therapy was found to be 80% (95% CI: 0.39-0.93, P = 0.004) in ESI and 91% (95% CI: 0.72-0.97, P < 0.0001) in peritonitis due to S. aureus; 70% (95% CI: 0.47-0.82, P < 0.0001) in ESI and 42% (95% CI: 0.25-0.55, P < 0.0001) in peritonitis due to all organisms among mupirocin-treated and -untreated subjects. Based on the three randomized controlled trials, ESI and peritonitis due to S. aureus were found to be reduced by 73% (95% CI: 0.63-0.80, P < 0.0001) and 40% (95% CI: 0.17-0.56, P = 0.002), respectively. Interestingly, although mupirocin treatment can reduce the risk rate of ESI by 46% (95% CI: 0.35-0.55, P < 0.00001), it cannot decrease the risk rate of peritonitis due to all organisms (P = 0.56).
CONCLUSIONS
Mupirocin prophylaxis was effective on preventing ESI and peritonitis due to S. aureus and other organisms in PD patients.
Topics: Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Humans; Mupirocin; Peritoneal Dialysis; Peritonitis; Randomized Controlled Trials as Topic
PubMed: 19679557
DOI: 10.1093/ndt/gfp411 -
American Journal of Health-system... Oct 1997The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of mupirocin are reviewed. Mupirocin is a naturally occurring... (Review)
Review
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.
Topics: Administration, Intranasal; Adult; Anti-Bacterial Agents; Cross Infection; Humans; Infection Control; Methicillin Resistance; Mupirocin; Rhinitis; Staphylococcal Infections; Staphylococcus aureus
PubMed: 9331438
DOI: 10.1093/ajhp/54.19.2185 -
Applied Microbiology and Biotechnology Apr 2011Mupirocin is a polyketide antibiotic produced by Pseudomonas fluorescens. The biosynthetic cluster encodes 6 type I polyketide synthase multifunctional proteins and 29... (Review)
Review
Mupirocin is a polyketide antibiotic produced by Pseudomonas fluorescens. The biosynthetic cluster encodes 6 type I polyketide synthase multifunctional proteins and 29 single function proteins. The biosynthetic pathway belongs to the trans-AT group in which acyltransferase activity is provided by a separate polypeptide rather than in-cis as found in the original type I polyketide synthases. Special features of this group are in-cis methyltransferase domains and a trans-acting HMG-CoA synthase-cassette which insert α- and β- methyl groups respectively while enoyl reductase domains are absent from the condensing modules. In addition, for the mupirocin system, there is no obvious loading mechanism for initiation of the polyketide chain and many aspects of the pathway remain to be elucidated. Mupirocin inhibits isoleucyl-tRNA synthetase and has been used since 1985 to help prevent infection by methicillin-resistant Staphylococcus aureus, particularly within hospitals. Resistance to mupirocin was first detected in 1987 and high-level resistance in S. aureus is due to a plasmid-encoded second isoleucyl-tRNA synthetase, a more eukaryotic-like enzyme. Recent analysis of the biosynthetic pathway for thiomarinols from marine bacteria opens up possibilities to modify mupirocin so as to overcome this resistance.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Bacterial Proteins; Humans; Mupirocin; Pseudomonas fluorescens
PubMed: 21336932
DOI: 10.1007/s00253-011-3128-3 -
The Cochrane Database of Systematic... Oct 2008Staphylococcus aureus (S. aureus) is the leading nosocomial (hospital acquired) pathogen in hospitals throughout the world. Traditionally, control of S. aureus has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Staphylococcus aureus (S. aureus) is the leading nosocomial (hospital acquired) pathogen in hospitals throughout the world. Traditionally, control of S. aureus has been focused on preventing cross-infection between patients, however, it has been shown repeatedly that a large proportion of nosocomial S. aureus infections originate from the patient's own flora. Nasal carriage of S. aureus is now considered a well defined risk factor for subsequent infection in various groups of patients. Local antibiotic treatment with mupirocin ointment is often used to eradicate nasal S. aureus.
OBJECTIVES
To determine whether the use of mupirocin nasal ointment in patients with identified S. aureus nasal carriage reduced S. aureus infection rates.
SEARCH STRATEGY
We searched the Cochrane Wounds Group Specialised Register (May 2008), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2 2008), MEDLINE (1950 to May 2008), EMBASE (1980 to May 2008) and CINAHL (1982 to May 2008). To identify unpublished trials, abstract books from major scientific meetings (ICAAC, ESCMID and SHEA) were handsearched, researchers and manufacturers of mupirocin were contacted and other electronic databases were searched (SIGLE, ASLIB Index, mRCT, USA Clinical Trials).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing nasal mupirocin with no treatment or placebo or alternative nasal treatment in the prevention of S. aureus infections in nasal S. aureus carriers were included.
DATA COLLECTION AND ANALYSIS
Titles, abstracts and full-text articles of studies retrieved from the search process were independently assessed by two authors for inclusion. From included studies a data extraction form was made and the quality of the trial was assessed. The primary outcome was the S. aureus infection rate (any site). Secondary outcomes were time to infection, mortality, adverse events and infection rate caused by micro-organisms other than S. aureus.
MAIN RESULTS
Nine RCTs involving 3396 participants met the inclusion criteria. Patient populations varied and several types of nosocomial S. aureus infection were described including bacteraemia, exit-site infections, peritonitis, respiratory tract infections, skin infections, surgical site infections (SSI) and urinary tract infections. After pooling the eight studies that compared mupirocin with placebo or with no treatment, there was a statistically significant reduction in the rate of S. aureus infection associated with intranasal mupirocin (RR 0.55, 95% CI 0.43 to 0.70).A planned subgroup analysis of surgical trials demonstrated a significant reduction in the rate of nosocomial S. aureus infection rate associated with mupirocin use (RR 0.55, 95% CI 0.34 to 0.89) however this effect disappeared if the analysis only included surgical site infections caused by S. aureus (RR 0.63, 95% CI 0.38 to 1.04), possibly due to a lack of power. The infection rate caused by micro-organisms other than S. aureus was significantly higher in patients treated with mupirocin compared with control patients (RR 1.38 95% CI 1.118 to 1.72).
AUTHORS' CONCLUSIONS
In people who are nasal carriers of S. aureus, the use of mupirocin ointment results in a statistically significant reduction in S. aureus infections.
Topics: Administration, Intranasal; Anti-Bacterial Agents; Carrier State; Humans; Mupirocin; Nose; Ointments; Randomized Controlled Trials as Topic; Staphylococcal Infections; Staphylococcus aureus
PubMed: 18843708
DOI: 10.1002/14651858.CD006216.pub2