Fabrication of Mupirocin-Loaded Nanostructured Lipid Carrier and Its In Vitro Characterization.

In the present study, mupirocin (MP), an antimicrobial agent, was formulated as a nanostructured lipid carrier (NLC) by using a novel method named as melt emulsion ultrafiltration method. For the formulation of NLC, glyceryl monostearate and watermelon seed oil were used as solid and liquid lipids, respectively. The method was optimized for various parameters by Taguchi design of experiment and prepared NLCs were characterized for particle size, polydispersity index (PDI), shape, zeta potential, % drug loading, and in vitro release profile. The optimized NLCs were found to be smooth, monodisperse with PDI 0.229 ± 0.093. NLCs were found to have an average particle size of 139 ± 0.75 nm and +21.9 ± 0.98 mV as zeta potential. The % drug loading of optimized NLCs was found to be 59% ± 0.13%. The optimized NLCs were able to release the drug up to 24 h. The release kinetic study revealed mixed-order kinetics. Hence, it was concluded that the novel method is simple and able to fabricate MP-loaded NLCs with sustained release property and being stable in terms of particle size, PDI, and % drug loading.

Interventions for preventing mastitis after childbirth.

BACKGROUND: Despite the health benefits of breastfeeding, initiation and duration rates continue to fall short of international guidelines. Many factors influence a woman's decision to wean; the main reason cited for weaning is associated with lactation complications, such as mastitis. Mastitis is an inflammation of the breast, with or without infection. It can be viewed as a continuum of disease, from non-infective inflammation of the breast to infection that may lead to abscess formation. OBJECTIVES: To assess the effectiveness of preventive strategies (for example, breastfeeding education, pharmacological treatments and alternative therapies) on the occurrence or recurrence of non-infective or infective mastitis in breastfeeding women post-childbirth. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 October 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials of interventions for preventing mastitis in postpartum breastfeeding women. Quasi-randomised controlled trials and trials reported only in abstract form were eligible. We attempted to contact the authors to obtain any unpublished results, wherever possible.  Interventions for preventing mastitis may include: probiotics, specialist breastfeeding advice and holistic approaches.   DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 10 trials (3034 women). Nine trials (2395 women) contributed data. Generally, the trials were at low risk of bias in most domains but some were high risk for blinding, attrition bias, and selective reporting. Selection bias (allocation concealment) was generally unclear. The certainty of evidence was downgraded due to risk of bias and to imprecision (low numbers of women participating in the trials). Conflicts of interest on the part of trial authors, and the involvement of industry funders may also have had an impact on the certainty of the evidence. Most trials reported our primary outcome of incidence of mastitis but there were almost no data relating to adverse effects, breast pain, duration of breastfeeding, nipple damage, breast abscess or recurrence of mastitis. Probiotics versus placebo Probiotics may reduce the risk of mastitis more than placebo (risk ratio (RR) 0.51, 95% confidence interval (CI) 0.35 to 0.75; 2 trials; 399 women; low-certainty evidence). It is uncertain if probiotics reduce the risk of breast pain or nipple damage because the certainty of evidence is very low. Results for the biggest of these trials (639 women) are currently unavailable due to a contractual agreement between the probiotics supplier and the trialists. Adverse effects were reported in one trial, where no woman in either group experienced any adverse effects. Antibiotics versus placebo or usual care The risk of mastitis may be similar between antibiotics and usual care or placebo (RR 0.37, 95% CI 0.10 to 1.34; 3 trials; 429 women; low-certainty evidence). The risk of mastitis may be similar between antibiotics and fusidic acid ointment (RR 0.22, 95% CI 0.03 to 1.81; 1 trial; 36 women; low-certainty evidence) or mupirocin ointment (RR 0.44, 95% CI 0.05 to 3.89; 1 trial; 44 women; low-certainty evidence) but we are uncertain due to the wide CIs. None of the trials reported adverse effects. Topical treatments versus breastfeeding advice The risk of mastitis may be similar between fusidic acid ointment and breastfeeding advice (RR 0.77, 95% CI 0.27 to 2.22; 1 trial; 40 women; low-certainty evidence) and mupirocin ointment and breastfeeding advice (RR 0.39, 95% CI 0.12 to 1.35; 1 trial; 48 women; low-certainty evidence) but we are uncertain due to the wide CIs. One trial (42 women) compared topical treatments to each other. The risk of mastitis may be similar between fusidic acid and mupirocin (RR 0.51, 95% CI 0.13 to 2.00; low-certainty evidence) but we are uncertain due to the wide CIs. Adverse events were not reported. Specialist breastfeeding education versus usual care The risk of mastitis (RR 0.93, 95% CI 0.17 to 4.95; 1 trial; 203 women; low-certainty evidence) and breast pain (RR 0.93, 95% CI 0.36 to 2.37; 1 trial; 203 women; low-certainty evidence) may be similar but we are uncertain due to the wide CIs. Adverse events were not reported. Anti-secretory factor-inducing cereal versus standard cereal The risk of mastitis (RR 0.24, 95% CI 0.03 to 1.72; 1 trial; 29 women; low-certainty evidence) and recurrence of mastitis (RR 0.39, 95% CI 0.03 to 4.57; 1 trial; 7 women; low-certainty evidence) may be similar but we are uncertain due to the wide CIs. Adverse events were not reported. Acupoint massage versus routine care Acupoint massage probably reduces the risk of mastitis compared to routine care (RR 0.38, 95% CI 0.19 to 0.78;1 trial; 400 women; moderate-certainty evidence) and breast pain (RR 0.13, 95% CI 0.07 to 0.23; 1 trial; 400 women; moderate-certainty evidence). Adverse events were not reported. Breast massage and low frequency pulse treatment versus routine care Breast massage and low frequency pulse treatment may reduce risk of mastitis (RR 0.03, 95% CI 0.00 to 0.21; 1 trial; 300 women; low-certainty evidence). Adverse events were not reported. AUTHORS' CONCLUSIONS: There is some evidence that acupoint massage is probably better than routine care, probiotics may be better than placebo, and breast massage and low frequency pulse treatment may be better than routine care for preventing mastitis. However, it is important to note that we are aware of at least one large trial investigating probiotics whose results have not been made public, therefore, the evidence presented here is incomplete. The available evidence regarding other interventions, including breastfeeding education, pharmacological treatments and alternative therapies, suggests these may be little better than routine care for preventing mastitis but our conclusions are uncertain due to the low certainty of the evidence. Future trials should recruit sufficiently large numbers of women in order to detect clinically important differences between interventions and results of future trials should be made publicly available.

Development of Emulgel Delivery of Mupirocin for Treatment of Skin Infection.

AIM: To design controlled release topical delivery of mupirocin for the treatment of skin infection. BACKGROUND: Mupirocin is an antibacterial drug. Mupirocin works to kill the bacteria, which include strains of Staphylococcus aureus and Streptococcus pyogenes. It is also used for the treatment of inflammation of a hair follicle. The half-life of mupirocin is only 20-40 min. It has very slight solubility in water. Patent literature had shown work on ointment, antibiotic composition, nasal and topical composition. Emulgel is a duel control release system for the topical delivery of hydrophobic drugs. OBJECTIVE: The objective was to formulate emulgel with controlled delivery of mupirocin using Sepineo P 600. METHODS: Soya oil, tween 80 and polyethylene glycol 400 (Oil:Surfactant:Cosurfactant) were used for emulsion formulation. Emulgel was optimized by 32 factorial design. Sepineo P 600 and hydroxy propyl methyl cellulose K4M were used as independent variables. Drug excipient compatibility analysis was carried out by FTIR, UV and DSC spectra. Emulgel was evaluated for its physical characterization, in vitro release, ex vivo release, antimicrobial and anti-inflammatory study. RESULTS: DSC, UV and FTIR analysis confirmed drug excipient compatibility. FE SEM showed a size range between 228-255 nm. Zeta potential was found to be -25.1 mV, which showed good stability of the emulsion. Design expert software showed F2 as an optimized batch. Release studies indicated that the controlled release of drugs forms Sepineo P 600 gel due to its higher gelling capacity. Batch F2 showed comparable results with marketed formulation against Staphylococcus aureus. For batch F2, 40 µg/ml was the minimal inhibitory concentration. CONCLUSION: Antimicrobial and anti-inflammatory study proved successful development of stably controlled release mupirocin emulgel.

Topical co-administration of Teucrium polium hydroethanolic extract and Aloe vera gel triggered wound healing by accelerating cell proliferation in diabetic mouse model.

Diabetic wounds are major issues in patients with diabetes. Medicinal plants of Teucrium polium and Aloe vera have antioxidant and anti-inflammatory properties that may be profitable for diabetic patients. This study was conducted to evaluate the effect of co-administration of ointments prepared from Teucrium polium hydroethanolic extract (TPEO) and Aloe vera gel (AVGO) on excisional wound healing in a diabetic mouse model. Following the induction of diabetes and circular excisional wound (7 mm), the mice were divided into six groups, namely (Ⅰ) control mice treated with mupirocin (as a standard drug), (Ⅱ and Ⅲ) the mice treated with 5 and 10 % TPEO, (Ⅳ and Ⅴ) the mice treated with 5 and 10 % AVGO, and (Ⅵ) the mice treated with a combination of 5% TPEO and 5% AVGO (TPEO+AVGO). To investigate the wound area, we further evaluated the wound area ratio, histological analysis and the serum levels of tissue antioxidant capacity (TAC) and malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), immunohistochemistry staining for vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), glucose transporter-1(GLUT-1) and collagen type 1 and mRNA expression levels for VEGF, IGF-1, GLUT-1 and fibroblast growth factor-2 (FGF-2). The results showed that administration of the ointments, especially in combination form, shortened the inflammatory phase and reduced the levels of tissue MDA, TNF-α and IL-1ß compared to mupirocin group (P < 0.05). Moreover, fibroblasts proliferation, collagen deposition, VEGF, IGF-1, GLUT-1-positive cells and level of TAC, and expressions of VEGF, IGF-1, GLUT-1 and FGF-2 were significantly (P < 0.05) increased in TPEO and AVGO, and especially in the mice treated with the mixed form. Therefore, topical co-administration of TPEO + AVGO accelerated open diabetic wound healing through shortening the inflammatory phase and increasing cell proliferation and collagen deposition.

Liposomal mupirocin holds promise for systemic treatment of invasive Staphylococcus aureus infections.

Staphylococcus aureus is a major cause of severe invasive infections. The increasing incidence of infections caused by antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA), calls for exploration of new approaches to treat these infections. Mupirocin is an antibiotic with a unique mode of action that is active against MRSA, but its clinical use is restricted to topical administration because of its limited plasma stability and rapid degradation to inactive metabolites. Mupirocin was identified by a machine learning approach to be suitable for nano-liposome encapsulation. The computational predictions were verified experimentally and PEGylated nano-liposomal formulation of mupirocin (Nano-mupirocin) was developed. The aim of this study was to investigate the efficacy of this formulation when administered parenterally for the treatment of S. aureus invasive infections. Nano-mupirocin exhibited prolonged half-life of active antibiotic and displayed superior antimicrobial activity against S. aureus than free mupirocin in the presence of plasma. Parenteral application of Nano-mupirocin in a murine model of S. aureus bloodstream infection resulted in improved antibiotic distribution to infected organs and in a superior therapeutic efficacy than the free drug. Parenterally administered Nano-mupirocin was also more active against MRSA than free mupirocin in a neutropenic murine lung infection model. In addition, Nano-mupirocin was very efficiently taken up by S. aureus-infected macrophages via phagocytosis leading to enhanced delivery of mupirocin in the intracellular niche and to a more efficient elimination of intracellular staphylococci. The outcome of this study highlights the potential of Nano-mupirocin for the treatment of invasive MRSA infections and support the further clinical development of this effective therapeutic approach.

Development, characterization and pharmacokinetics of mupirocin-loaded nanostructured lipid carriers (NLCs) for intravascular administration.

Mupirocin is a promising broad-spectrum antibiotic that is effective in treating MRSA infections. However, due to its rapid elimination and hydrolysis following injection and high protein binding, current therapeutic use is limited to topical administration. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug degradation by encapsulation. The objective of this research is to develop and characterize Mupirocin-Loaded Nanostructured Lipid Carriers (M-NLC) for intravascular administration. The MNLC was produced by a combination of high shear homogenization and high pressure homogenization of solid (cetyl palmitate) and liquid (caprylic/caprylic acid) biocompatible lipids in 5 different ratios. The mean particle size, polydispersity index (PDI) and the zeta potential (ZP) of the MNLC formulations were between 99.8 and 235 nm, PDI lower than 0.164, ZP from -25.96 to -19.53 and pH ranging from 6.28-6.49. The MNLC formulation also enhances the anti-bacterial activity of mupirocin. All formulation showed sustained drug release and good physical characteristics for three months storage under 25 °C. It also revealed that the MNLC 1 is safe at 250 mg/kg dose in rats. The MNLC 1 also showed a significant increase in plasma concentration in rabbits following IV administration thus, demonstrating an enhancement on its pharmacokinetic profile as compared to free mupirocin.

Tratamiento de la enfermedad de Hailey-Hailey generalizada con fototerapia UVB de banda estrecha / Narrowband UV-B Phototherapy in the Treatment of Generalized Hailey-Hailey Disease

No disponible

[Topical ozone therapy: An innovative solution to patients with herpes zoster].

OBJECTIVE: To observe the clinical efficacy and safety of topical ozone therapy for patients with herpes zoster by reflectance confocal microscopy (RCM).
 Methods: A total of 60 patients with herpes zoster were divided into a control group and an ozone treatment group (n=30). In the control group, patients took oral valacyclovir tablets or granules (0.3 g per day, three times a day) and they were subjected to local weak laser irradiation treatment plus topical 2% mupirocin ointment twice a day. In the ozone group, the treatment is same as the control group except mupirocin ointment was replaced with topical ozone treatment (hydrotherapy every day plus ozonated oil twice a day). The clinical symptoms, discoid cell and adverse reactions were observed and taken records at day 0, 3, 7 and 14. Statistical analysis was performed to compare the clinical efficacy between the 2 groups. 
 Results: On the seventh day of treatment, the discoid cells of the ozone group disappeared, and the difference between the control group and the ozone group was statistically significant (P<0.05). The difference of decreased percentage of pain scores at each time point between the 2 groups was statistically significant (P<0.05). The clinical efficacy was 100% in the ozone group and 86.7% in the control group, with significant difference between the 2 groups (P<0.05).
 Conclusion: Topical ozone therapy in patients with herpes zoster is helpful in relieving pain, shortening the course as well as improving the clinical efficacy without obvious adverse reactions. It is worth to be popularized.

Topical therapy for refractory rhinosinusitis caused by methicillin-resistant Staphylococcus aureus: First report in a prospective series.

OBJECTIVE: The incidence of refractory chronic rhinosinusitis (CRS) associated with methicillin-resistant Staphylococcus aureus (MRSA) is rising and remains a therapeutic challenge. The goal of this study is to demonstrate the efficacy of a non-invasive topical therapy against MRSA in these patients. METHODS: Seventeen patients with refractory CRS caused by MRSA were treated with a topical therapy protocol. Treatment consisted of weekly endoscopic sinus debridement followed by intra-sinus installation of a hydroxyl-ethylcellulose gel that releases mometasone and a culture-directed antibiotic for a period of 6 weeks, along with daily nasal nebulization of mometasone with the same antibiotic and saline rinses. Clinical outcome was assessed using the Lund-Kennedy (LK) symptom and endoscopic appearance scores. Sinus mucosal tissue was homogenized and cultured, and microbial biofilm burden was assessed based on colony forming units (CFUs) counts. RESULTS: Rhinotopic therapy resulted in clearance of MRSA in 13 of 16 patients (81.2%). Treated patients also demonstrated significant improvement clinically as measured by the LK scores. In addition, a significant decrease in mucosal CFUs was observed post-therapy. CONCLUSION: Our findings demonstrate that topical therapy is an effective method for treating MRSA-associated refractory CRS.

Zoon Balanitis Revisited: Report of Balanitis Circumscripta Plasmacellularis Resolving With Topical Mupirocin Ointment Monotherapy.

INTRODUCTION: Zoon balanitis is an idiopathic benign inflammatory condition of the glans penis and prepuce. A patient with biopsy confirmed diagnosis of Zoon balanitis who was successfully treated with topical mupirocin ointment monotherapy is described.

METHOD: A search using PubMed database was performed using the following terms: Zoon balanitis (cases, diagnosis, treatment of), balanitis circumscripta plasmacellularis, and mupirocin. Relevant papers and their reference citations were reviewed and evaluated.

RESULTS: The gold standard of treatment for Zoon balanitis has previously been circumcision. More recently, topical calcineurin inhibitors have been shown to be effective. Our patient had successful resolution of his Zoon balanitis after 3 months of mupirocin ointment monotherapy.

DISCUSSION: Zoon balanitis is a benign inflammatory dermatosis. Previous successful treatment modalities include circumcision, phototherapy, laser therapy, and topical calcineurin inhibitors. Topical mupirocin ointment twice daily resulted in resolution of Zoon balanitis in our patient. Additional evaluation of mupirocin ointment as a therapeutic agent should be considered as a potential first-line therapy in patients with Zoon balanitis.

J Drugs Dermatol. 2017;16(3):285-287.

Alteration in Bacterial Culture After Treatment With Topical Mupirocin for Recalcitrant Chronic Rhinosinusitis.

IMPORTANCE: Topical mupirocin therapy is used to treat symptomatic chronic sinusitis (CRS). However, the potential adverse impact of this therapy on the sinus microbiota has not been well quantified. OBJECTIVE: To determine changes in microbiologic culture results before and after topical mupirocin therapy in patients with CRS with medically and surgically refractory disease. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective medical chart review for 22 consecutive adults evaluated and treated between January 1, 2012, and January 1, 2014, at an otolaryngology-rhinology clinic at a regional academic medical center. The patients were 14 men and 8 women, who had undergone functional endoscopic sinus surgery for CRS, and in whom sinus aspirate cultures were performed before and after topical mupirocin therapy for symptomatic disease. Analyses were performed in April 2014. EXPOSURES: Patients underwent treatment with saline sinus rinse, with the addition of mupirocin, for at least 1 week. MAIN OUTCOMES AND MEASURES: Bacterial isolates from sinus aspirate culture. RESULTS: The patients included 14 men and 8 women, 18 to 75 years old, who underwent a mean of 1.9 functional endoscopic sinus surgical procedures. The mean (range) duration of mupirocin therapy was 6 (2-12) weeks. Before mupirocin therapy, cultures from symptomatic patients (14 men and 8 women, ages 18-75 years) revealed common bacteria implicated in CRS, which are characteristically gram-positive. After mupirocin therapy, cultures from symptomatic patients shifted significantly: 19 were gram-positive vs 3 gram-negative before treatment; 9 were gram-positive vs 13 gram-negative after treatment (P = .004), with increased growth of pathogenic gram-negative bacteria and Corynebacterium. CONCLUSIONS AND RELEVANCE: These data present evidence supporting the distinct abrogation of culturable sinus bacteria after mupirocin rinses, identifying a shift toward increased pathogenic bacteria. Consideration of healthy host microbiome and immune dysfunction should guide future treatment considerations.

Comparative analysis of MRSA strains isolated from cases of mupirocin ointment treatment in which eradication was successful and in which eradication failed.

Nasal decolonization in methicillin-resistant Staphylococcus aureus (MRSA) carriers using mupirocin (MUP) is a strategy that complements barrier precautions and contact isolation. However, eradication failure cases have been observed despite isolates being susceptible to MUP. This would suggest that the minimum inhibitory concentration (MIC) alone is not the only determinant of successful eradication. In this study, we undertook a comparative analysis of MRSA isolates from cases of successful and unsuccessful MUP-eradication treatment. The analyses we carried out were: determination of mupirocin MICs, sequencing of the isoleucyl-tRNA synthetase (ileS) gene, staphylococcal cassette chromosome mec typing, and the assessment of slime production. MICs for all 14 of the successful nasal decolonization cases showed susceptibility to MUP, whereas 21 (87.5 %) of the 24 unsuccessful cases were MUP-susceptible, with low-level resistance seen in 3 (12.5 %) strains. In the analysis of mutations in the ileS gene, one strain with an MIC of 4 µg/ml exhibited a G1778A point mutation that has not been previously reported. In the 14 successful nasal decolonization cases, only 1 strain (7.1 %) was an MRSA slime-producer, compared with 19 (79.7 %) of the 24 MRSA strains that could not be eradicated after MUP treatment (p < 0.05). For the eradication of MRSA by MUP, it is possible that slime may affect drug penetration. In conclusion, slime production was the only significant difference between isolates recovered from successful and unsuccessful eradication cases.

Interventions for preventing mastitis after childbirth.

BACKGROUND: Despite the health benefits of breastfeeding, initiation and duration rates continue to fall short of international guidelines. Many factors influence a woman's decision to wean; the main reason cited for weaning is associated with lactation complications, such as mastitis. OBJECTIVES: To assess the effects of preventive strategies for mastitis and the subsequent effect on breastfeeding duration. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (8 August 2012). SELECTION CRITERIA: We included randomised controlled trials of interventions for preventing mastitis in postpartum breastfeeding women. DATA COLLECTION AND ANALYSIS: We independently identified relevant studies and assessed the trial quality. We contacted trial authors for missing data and information as appropriate. MAIN RESULTS: We included five trials (involving 960 women). In three trials of 471 women, we found no significant differences in the incidence of mastitis between use of antibiotics and no antibiotics (risk ratio (RR) 0.43; 95% confidence interval (CI) 0.11 to 1.61; or in one trial of 99 women comparing two doses (RR 0.38; 95% CI 0.02 to 9.18). We found no significant differences for mastitis in three trials of specialist breastfeeding education with usual care (one trial); anti-secretory factor cereal (one trial); and mupirocin, fusidic acid ointment or breastfeeding advice (one trial).Generally we found no differences in any of the trials for breastfeeding initiation or duration; or symptoms of mastitis. AUTHORS' CONCLUSIONS: There was insufficient evidence to show effectiveness of any of the interventions, including breastfeeding education, pharmacological treatments and alternative therapies, regarding the occurrence of mastitis or breastfeeding exclusivity and duration. While studies reported the incidence of mastitis, they all used different interventions. Caution needs to be applied when considering the findings of this review as the conclusion is based on studies, often with small sample sizes. An urgent need for further adequately powered research is needed into this area to conclusively determine the effectiveness of these interventions.

[Is it necessary to know which workers are carriers of MRSA in contact with cancer patients?]. / ¿Es necesario conocer qué trabajadores son portadores de SARM en contacto con enfermos oncológicos?

Our objective was to determine the prevalence of methicillin-resistant Staphylococcus aureus in workers who had direct contact with oncologic patients infected with MRSA and admitted to the intensive care unit of the Valencian Institute of Oncology. A study of prevalence of MRSA colonization of 62 workers was performed. Samples were taken from nose and pharynx in each of the workers. After 24 hours of incubation in Amies transport medium Viscose (Eurotubo®), 124 samples were seeded (N = 124) in chocolate agar agar, MRSA II and BHI broth (Brain Heart Infusion). Those colonies that were identified by Gram stain gram-positive cocci in clusters available, catalase positive and coagulase positive were processed for study of sensitivity by Kirby-Bauer method and screening test for methicillin (10µg of Oxoid®) on Mueller-Hinton (Becton-Dickinson®, BD), supplemented with NaCl (2%). Those confirmed MRSA isolates, he returned to perform sensitivity study by microdilution (MicroScan®, Siemens) to determine the MIC (mg/L). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was 1.61% (1) and 12.90% (8) for methicillin-sensitive Staphylococcus aureus (MSSA), from nostrils. The measures implemented were: nasal application of mupirocin to the worker colonized control isolation measures in infected patients and indoctrination of the personnel involved.

Agents for the decolonization of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are a common cause of hospital- and community-acquired infections. Persons may have asymptomatic colonization with MRSA in the nares, axillae, perineum, or groin. Since MRSA colonization often precedes infection, and infection is associated with significant morbidity and mortality, there is great interest in preventing the transmission of MRSA and decolonizing persons who harbor these bacteria. We provide an evidence-based review of MRSA decolonization agents. Our search strategy included the databases of the Cochrane Central Register of Controlled Trials, MEDLINE (1962-May 2008), and EMBASE (1980-May 2008). To identify unpublished trials, abstract books from appropriate major scientific meetings were hand searched, manufacturers were contacted, and pharmacology references were researched for available commercial products, formulations, adverse events, and dosing. The most extensive research in MRSA decolonization has been conducted with mupirocin, which is applied to the anterior nares 2-3 times/day for 5 days. Increased use is correlated to resistance development; therefore, routine decolonization is not prudent unless MRSA colonization is confirmed in the nares or other site. Retapamulin is under investigation for use in nares decolonization. If total body decolonization is necessary, bathing or showering with an antiseptic agent such as chlorhexidine gluconate is recommended in combination with mupirocin applied to the nares to improve the likelihood of eradication. Oral antibiotics have been evaluated for use in decolonization of the skin and nares but should be considered only in conjunction with topical agents and when all other decolonization attempts and environmental controls have been exhausted. Homeopathic and investigational agents may also be effective. Although mupirocin is the standard of care for decolonization of MRSA, several agents demonstrate efficacy and many merit further investigation.

Antibacterial activity of propolis against MRSA and synergism with topical mupirocin.

OBJECTIVES: The aim of the present study was to investigate the activity of the propolis and its combinations with mupirocin against methicillin-resistant Staphylococcus aureus (MRSA) in nasal carriage. METHODS: This study was carried out between June and August 2005. To infect nares of the rabbits, MRSA (ATCC 33591) strain was used. Minimum inhibitory concentration was determined according to National Committee for Clinical Laboratory Standards. Each inoculum was prepared in the same medium at a density adjusted to a 0.5 McFarland turbidity standard (10(5) colony-forming units [cfu]/mL) and diluted 1:100 for the broth microdilution procedure. Ten microliters (10 microL) (10(5) cfu/mL) of the bacterial suspension containing approximately 1000 cfu of MRSA was administered with sterile microsyringe through both nostrils of each rabbit. Ninety-six (96) hours after inoculation, the presence of infection was confirmed by using bacterial cultures. Twenty-six young New Zealand rabbits were randomly divided into 4 groups. Each treatment group (1, 2, and 3) included 7 rabbits and control group (group 4) included 5 rabbits. Group 1 was treated with topical mupirocin + ethanolic extract of propolis drops, group 2 received topical mupirocin, group 3 was administered ethanolic extract of propolis drops, and the control group (group 4) was only treated with phosphate-buffered solution drops for 7 days. At the end of study, nasal cultures and smears were obtained for bacterial count and cytologic examination. RESULTS: The colony numbers of bacteria in group 1 were determined to be significantly lower than in group 2 (p = 0.0001), group 3 (p = 0.0001), and group 4 (p = 0.0001). The mean bacterial cell counts of groups 1-4 were 360.2 +/- 52.4 cfu/mL, 4120.6 +/- 860.4 cfu/mL, 5980.8 +/- 1240.6 cfu/mL, and 11500.0 +/- 2568.4 cfu/mL, respectively. Mupirocin + propolis administration (group 1) resulted in a significant reduction in the polymorphonuclear leukocyte (PMNL) count in the mucous membranes of rabbits compared with the other treatment groups (p < 0.05). CONCLUSIONS: Propolis addition to mupirocin regimen was found to result in more profound reduction in bacterial cell count and inflammatory response compared with the rest of the treatment modalities.

Successful termination of a furunculosis outbreak due to lukS-lukF-positive, methicillin-susceptible Staphylococcus aureus in a German village by stringent decolonization, 2002-2005.

BACKGROUND: Skin infections due to Staphylococcus aureus have recently become a public concern, mainly because of emerging resistance against widely used antibiotics and specific virulence determinants. Strains harboring the lukS-lukF gene (which codes for Panton-Valentine leukocidin) are frequently associated with severe furunculosis. Generally applicable strategies for the control of community outbreaks of furunculosis have not been defined. METHODS: We report the investigation and successful termination of an outbreak of furunculosis due to lukS-lukF-positive S. aureus in a German village (n=144). Nasal swab specimens were obtained from village residents. A retrospective cohort study was conducted. Nasally colonized persons, persons who had current furuncles or who had experienced relapsing furuncles since 2002, and their family members underwent stringent decolonization measures using mupirocin nasal ointment and disinfecting wash solution. Multiple nasal swab specimens were obtained to monitor the long-term outcome of decolonization measures. RESULTS: From January 1998 through December 2004, 42 cases and 59 relapses of furunculosis were identified by active case finding. Of 140 participants tested, 51 (36%) were found to be nasally colonized with S. aureus. In 9 participants, the strain was positive for lukS-lukF. No methicillin resistance was detected. Risk of furunculosis was associated with contact with case patients (relative risk, 6.8; 95% confidence interval, 3.2-14.3) and nasal colonization with a lukS-lukF-positive strain of S. aureus (relative risk, 3.6; 95% confidence interval, 2.3-5.9). Passive surveillance implemented in January 2005 did not detect any case of lukS-lukF-positive, S. aureus-associated furuncles in this village. CONCLUSION: This report describes a successful strategy for terminating the transmission of epidemic strains of S. aureus among a nonhospitalized population.

Prevention of acquired infections in intubated patients with the combination of two decontamination regimens.

OBJECTIVE: The use of topical polymyxin and tobramycin to prevent intensive care infections is controversial. Moreover, these antibiotics are ineffective against methicillin-resistant Staphylococcus aureus. A decontamination regimen using mupirocin and chlorhexidine could prevent acquired infections, including those involving S. aureus. Because these two regimens could have a complementary role, we evaluated their effects when given both alone and combined. DESIGN: The authors conducted a multiple-center, placebo-controlled, randomized, double-blind study performed according to a 2 x 2 factorial design. SETTING: The study was conducted at three polyvalent medical intensive care units at university-affiliated hospitals in France. PATIENTS: Adult patients (age, > or =18 yrs) intubated for <48 hrs who were likely to be ventilated for >48 hrs. INTERVENTION: Two regimens were used: topical administration of polymyxin/tobramycin (or placebo) and nasal mupirocin with chlorhexidine body washing (or nasal placebo with liquid soap). The patients (n = 515) received polymyxin/tobramycin alone (n = 130), mupirocin/chlorhexidine alone (n = 130), both regimens (n = 129), or all placebos (n = 126) for the period of mechanical ventilation plus 24 hrs. MEASUREMENTS AND MAIN RESULTS: The incidence of total infections acquired from the date of randomization until the termination date of study treatments plus 48 hrs was assessed. There were fewer acquired infections with both regimens than with polymyxin/tobramycin alone (odds ratio, 0.44; 95% confidence interval, 0.26-0.75; p = .003), mupirocin/chlorhexidine alone (0.43; 0.25-0.73; p = .002), or all placebos (0.42; 0.25-0.72; p = .001). There were no differences between polymyxin/tobramycin alone (0.95; 0.59-1.54; p = .84) and mupirocin/chlorhexidine alone (0.98; 0.60-1.58; p = .92) vs. all placebos. The probability of freedom from infection was higher with both regimens than with polymyxin/tobramycin alone (p = .002), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). Infection rates were also significantly lower with both regimens than with polymyxin/tobramycin alone (p = .017), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). CONCLUSION: Acquired infections were substantially reduced by mupirocin/chlorhexidine plus polymyxin/tobramycin, whereas each regimen given alone was ineffective. Whether both regimens could increase Candida infections deserves further investigation.