Mupirocin Research Articles

IN VITRO ACTIVITY OF MUPIROCIN ON STAPHYLOCOCCAL NASAL CARRIERS AMONG HEALTH CARE PERSONNEL IN A TERTIARY CARE HOSPITAL, JAIPUR, INDIA.

Introduction: Mupirocin (pseudomonic acid A) is an antibacterial agent with topical usage and wonderful antistaphylococcal and antistreptococcal characteristics. The formulation for nasal usage has been permitted by the U.S. Food and Drug Administration to eradicate nasal infections in adults. Healthcare workers possessing S. aureus as healthy carriers can be major origin of infection for the admitted patients. The anterior nares have proved to be the major reservoir for strains of S. aureus in both adult and children masses. To determine the Objective: prevalence of mupirocin susceptibility in S. aureus, coagulase-negative staphylococci (CoNS) and MRSA species by disk diffusion. A total of 100 nasal swabs were collected from health care personnel, aseptically during Materials And Methods: the study period. All the swab samples were processed immediately and isolated by standard microbiological methods. Antibiotic susceptibility testing was done by Kirby-Bauer disc diffusion method. Carriage rat Results: e of staphylococci was found to be 51% (including 44% of S. aureus and 7% CoNS), out of 100 nasal swabs collected during the study period. Prevalence rate of MRSA is detected to be 60.7% (31/44) in the health care workers. A total of 13 MSSA were detected in the sample collected from the anterior nares and 5 cases of MRCoNS also observed. The present study shows that all the identied S. aureus isolates were susceptible to low level mupirocin (5µg) as well as high level mupirocin (200µg). Nasal carri Conclusions: age of S. aureus is a major threat for public health as they can disseminate the same to the patients as well as to their colleagues. To reduce the prevalence and antimicrobial resistance, emphasis should be given to aseptic precaution, protective measures and topical application of mupirocin for eradication of nasal carriage.

Designing electrospun shellac nanofibers with mupirocin using the Box-Behnken approach for topical wound care

This study attempted to develop shellac (SHL) nanofibers containing a topical antibiotic, mupirocin (MP), as an alternative wound healing material. The impacts of formulation and process parameters such as SHL concentration, MP content, and applied voltage on the morphology of fibers were examined based on a 33 Box-Behnken experimental design with triplicate center points. The results indicated that the amounts of polymeric SHL and encapsulated MP were considered factors affecting the morphology of fabricated fibers, including size and bead ratio. As the concentrations of SHL and MP increased, the large-sized fibers would be obtained. Meanwhile, the appearance of beads would be lessened with the enhanced amount of SHL. The excellent encapsulation of MP in SHL carrier was indicated by the high entrapment efficiency (88.12 ± 0.09% - 109.93 ± 3.23%) which might be possibly due to the ultrafine network and microporous structures of nanofibers and the good affinity of MP for entrapping between the polymeric SHL as referred to the results of the characterization study. According to the assay of antimicrobial activity, S. aureus, the leading cause of wound infection, was entirely killed since 5 min after exposure to the SHL nanofibers loaded with MP, and the regrowth of living S. aureus was not found throughout the next 6 h. Therefore, the SHL nanofibers containing MP seemed to be an effective wound dressing with high encapsulation efficiency and potential antimicrobial activity against S. aureus over a period of time.

Comparison of Conventional Wet Dressing and Vacuum Assisted Closure with Hypochlorous Acid Application in Fournier Gangrene Treatment

Background: Bacterial toxins cause local tissue damage and necrosis. This can continue until a significant amount of tissue becomes necrotic. Neutralization of bacterial toxins improves results. Low concentrations of Hypochlorous Acid can be antimicrobial without causing cytotoxicity in normal cells in the wound and surrounding tissues. In this study, we aimed to compare the results of patients treated with hypochlorous acid (0.01% w/v) through Vacuum Assisted Closure and with traditional wet dressing after surgical debridement due to Fournier Gangrene in our clinic. Materials and Methods: 73 patients treated for Fournier Gangrene between 2009-2019 in our clinic were evaluated retrospectively. The patients were divided into two groups: those who received Hypochlorous Acid with Vacuum Assisted Closure (Group A, n = 30) and those who received traditional wet dressing (Group B, n = 42) after the first debridement. Hypochlorous Acid (0.01% w/v), known to destroy bacteria and bacterial toxins, was administered to 30 patients with Fournier Gangrene in saline with a pH of 4-5, 5-6 times a day. Using Vacuum Assisted Closure, 5-10 ml of 0.01% Hypochlorous Acid was applied to the wound and aspirated. For wet dressing application, the wound was closed by applying mupirocin calcium and rifamycin to an appropriate number of wet sponges suitable for the wound surface and depth after cleansing the wound with sponges moistened with isotonic 3 times a day. The collected data were compared. P values smaller than 0.05 were considered significant. Results: The hospitalization time and wound healing time of 30 patients who received Hypochlorous Acid with Vacuum Assisted Closure were shorter (p <0.05), and the number of patients requiring secondary debridement was also lower (p <0.05). Conclusion: Hypochlorous Acid application with Vacuum Assisted Closure is an effective, successful and important postoperative treatment and wound care method that provides shorter hospital stay and faster recovery time. Toxicity and immune dysfunction due to bacterial toxins and toxins released from damaged cells can be alleviated with 0.01 Hypochlorous Acid application via Vacuum Assisted Closure. We recommend this method, which is easy to apply and inexpensive in certain Fournier Gangrene cases.

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model.

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p < 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p < 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment.

Optimization, characterization and in vivo evaluation of mupirocin nanocrystals for topical administration

Treatment of infectious skin conditions resulting from wounds and burns with topical antibiotics is challenging, particularly those caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). This is due to the formation of bacterial biofilms characterized by antimicrobial resistance. Mupirocin (MP), a widely used topical antibiotic, is active against gram-positive bacteria including MRSA. However, MP suffers from sub-optimal therapeutic efficacy due to its poor water-solubility and the significant rise in MP-resistant S. aureus. In this study, the physico-chemical characteristics of MP were modified through nanocrystallization to improve its therapeutic efficacy for the treatment of skin infections. Mupirocin-nanocrystals (MP-NC) were prepared using a nanoprecipitation technique and optimized using a D-optimal response surface design. The optimization of MP-NC produced ultra-small monodisperse spherical particles with a mean diameter of 70 nm and a polydispersity index of 0.2. The design resulted in two optimal MP-NC formulations that were evaluated by performing series of in vitro, ex vivo, microbiological, and in vivo studies. In-vitro results showed a 10-fold increase in the saturation solubility and a 9-fold increase in the dissolution rate of MP-NC. Ex vivo permeation studies, using pig ears skin, showed a 2-fold increase in the dermal deposition of MP-NC with the highest drug deposition occurring at 500-µm skin depth. Moreover, the optimal MP-NC formulations were lyophilized and incorporated into a 2% w/w cream. Microbiological studies revealed a 16-fold decrease in the minimum inhibitory concentration and the minimum bactericidal concentration of MP-NC. In vivo studies, using a rat excision burn wound model, demonstrated rapid and complete healing of infected burn wounds in rats treated with MP-NC cream in comparison to marketed Avoban ointment. Our results suggest that nanocrystallization of MP may provide an avenue through which higher levels of a topically applied MP can be permeated into the skin to reach relevant infectious areas and exert potential local antibacterial effects.

Stability-indicating RP-HPLC method development and validation for estimation of Mupirocin calcium in bulk and in pharmaceutical formulation

BackgroundA simple, rapid, sensitive and selective stability-indicating (RP-HPLC) method is suggested for the determination of Mupirocin calcium in bulk drug and in pharmaceutical formulation. Mupirocin calcium was eluted from a PrincetoneSPHER-100 C8 (250 × 4.6 mm, 5 µm) column with mobile phase consisting of methanol and water (75:25 v/v) pH adjusted to 4 with acetic acid. The gradient was optimized with a flow rate of 1 mL/min and a wavelength of 221 nm.ResultThe complete analytical method validation was successfully carried out as per ICH guidelines. The retrieval study was carried out at 80% to 120% level of working concentration, and results were in the range of 99 to 101%. The linearity was proven in range of 4–24 µg/mL of working concentration with linear regression curve (R2 = 0.999) with limits of detection (LOD) and quantitation (LOQ) being 0.35 and 1.08 µg/mL, respectively. The retention time for Mupirocin calcium was 5.09 min. The method shows good recoveries and intra-day and inter-day relative standard deviations were less than 2%. Validation parameters as ruggedness and robustness were also determined as per ICH guidelines and were found to be satisfactory. For stability study, the drug was exposed to various stress conditions such as acid, base, oxidation and sunlight as per recommendations of ICH guidelines.ConclusionThe developed HPLC method could be successfully used for the estimation of Mupirocin calcium in bulk and in Pharmaceutical formulation. The high recovery and low relative standard deviation confirm the suitability of proposed method that can be employed for the routine analysis in bulk and Pharmaceutical formulation.

Dynamics of the Catalytic Active Site of Isoleucyl tRNA Synthetase from Staphylococcus aureus bound with Adenylate and Mupirocin.

The development of new antimicrobial drugs is critically needed due to the alarming increase in antibiotic resistance in bacterial pathogens. The active sites of different bacterial aminoacyl tRNA synthetases (aaRS) are validated targets of antibiotics. At present, the only aaRS inhibitor approved is mupirocin (MRC) which targets bacterial isoleucyl tRNA synthetase (IleRS). The present work is aimed at understanding the lacunae of knowledge concerning the active site conformational dynamics in IleRS in the presence of inhibitor mupirocin. With this end in view, we have carried out classical molecular dynamics simulation and metadynamics simulations of the open state of IleRS from Staphylococcus aureus (SaIleRS), the closed state tripartite complex bound with cognate adenylate (Ile-AMP) and tRNA, the closed state tripartite complex bound with noncognate MRC, and the closed state tripartite complex bound with tRNA and MRC with mutated SaIleRS (V588F). The present simulation established a dynamic picture of SaIleRS complexed with cognate and the noncognate substrates which are completely consistent with crystallographic and biochemical studies and explain the existing lacunae of knowledge. The active site is significantly more compact in the Ile-AMP bound complex compared to the open state due to the closure of the KMSKS and HMGH loops and clamping down of the tRNA acceptor end near the active site gate. The present result shows that the unusual open conformational state of the KMSKS loop observed in the cognate substrate-bound complex in the crystal is due to crystallographic constraints. Although the mupirocin tightly fits the catalytic active site in the MRC-bound complex, the nonanoic acid moiety is partly exposed to the water. The KMSKS loop is pushed open in the MRC-bound complex to accommodate the noncognate MRC. New tunnels open up, extending to the editing site in the complex. Out of its three broad segments, the C12 to C17 segment, the conjugated segment, and the nonanoic moiety, the conjugated part of MRC binds most effectively with the active site of the MRC-bound complex. The aromatic residues packing around the C12 to C17 segment of MRC stabilize the tRNA hairpin conformation in a similar way as observed in the TrpRS. The V588F mutation is weakening the interaction between this region of the active site and weakens the binding of MRC in the active site. This result explains why the V588F mutation is responsible for low-level mupirocin resistance. The free energy of unbinding the conjugated segment (and C12 to C17 segment, as well) largely contributes to the total free energy of unbinding the MRC. The active site organization of IleRS from eukaryotic Candida albicans is compared with the bacterial IleRS active site to understand the low binding affinity in eukaryotic IleRS. The present study could be a starting point of future studies related to the development of effective drug binding in the SaIleRS.

Recent Advances in Mupirocin Delivery Strategies for the Treatment of Bacterial Skin and Soft Tissue Infection

Skin and soft tissue infections (SSTIs) have increased problematically in hospital and ambulatory settings due to the poor immunity of hosts and multidrug-resistant pathogens. Mupirocin (MUP), a global topical antibiotic, is used for the treatment of SSTIs caused by various pathogens due to its unique mechanism of action. However, the therapeutic efficiency of MUP is hampered due to the protein binding and drug resistance caused by frequent use. A combined report covering the various aspects of MUP, such as the synthesis of the novel formulation, loading of the drug, and application against various skin infections, is missing. This comprehensive review focuses on various novel drug delivery strategies such as composite biomaterials/scaffold, hydrogel dressings, liposomes, liposomal hydrogel, microparticles/microspheres, microsponges, nanocapsules, nanofibers, silicone-based adhesive patches, and topical sprays. The therapeutic effect of the MUP can be synergized by combining with other agents and using novel strategies. The objective is to enhance patient compliance, decrease the resistance, magnify the delivery of MUP, and overcome the limitations of conventional formulations. Moreover, the carriers/dressing materials are biocompatible, biodegradable, stimulate wound healing, protect the wound from external environmental contamination, adsorb the wound exudates, and are permeable to oxygen and moisture. This review will help researchers to explore further the treatment of various bacterial skin infections by using MUP-loaded novel formulations with better efficacy, utilizing the novel nanostructures or combinatorial methods.

Design and Development of Mupirocin Nanofibers as Medicated Textiles for Treatment of Wound Infection in Secondary Burns

The present study assessed the topical potential of nanofibers loaded with Mupirocin (MUP) for the treatment of burns. Nanofibers of MUP were composed of Polyvinyl Pyrrolidone (PVP), Gelatin Type-A, and Ethanol using two methods: Solvent casting and Electrospinning. Nanofibers were characterized for Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), Drug Content Studies, in-vitro drug permeation, antibacterial and stability studies. The FT-IR studies showed that the Electrospinning technique had a very good mixing of MUP with the polymer. SEM studies showed that the morphology of electrospinning nanofibers had diameters in the range of 70.41 nm- 406.83 nm. The thermal decomposition studies of optimized Nanofiber (E.S.1) were performed by DSC and TGA study and it was found that the formulation had high stability in high-temperature environments. Permeation studies showed that E.S.1 had the highest percentage amount and controlled release of the drug (90 %) up to 8 has compared to other formulations. Nanofibers prepared through the Electrospinning technique showed better antibacterial activity against Staphylococcus aureus as compared to the Solvent casting nanofibers. This research suggested that MUP loaded nanofibers can be potentially used as a topical drug delivery system for the treatment of burns.

Design, optimization and in-vivo characterization of mupirocin loaded nanostructured lipid carrier based gel for effective treatment of impetigo

Mupirocin is a broad-spectrum antibiotic effective in treatment of skin infection (Impetigo), but the poor bioavailability limits its use as a conventional dosage form such as tablets, ointment and cream. The present investigation was aimed to design, optimize and evaluate Mupirocin (MC) loaded nanostructured lipid carriers (NLCs) based gel for topical application. Excipients identified were screened for apposite material required for the formulation of NLCs using process variables as the determining factors. The preparation of nanostructured lipid carriers (NLCs) was optimized using 32 factorial design with two independent variables (solid: liquid lipid ratio and surfactant (%)) and two responses (particle size (nm), entrapment efficiency (%)) using hot high pressure homogenization method. The formulation was further characterized for zeta potential (mV), polydispersity index and morphology. The optimized NLC dispersion of Mupirocin (MC) was lyophilized and loaded in 0.75% w/v Carbopol 980 gel and was evaluated for pH, viscosity and drug content. Mupirocin (MC) loaded NLC based gel were characterized for ex-vivo drug permeation and compared with marketed (cream) preparation. Further, drug deposition, skin irritation and stability study was carried out as per ICH guidelines. The optimized formulation (F5) containing Glyceryl behenate: Oleic acid (70:30), and Poloxamer 188 (0.5%) demonstrated smaller particle size (150.02 ± 1.52 nm) with higher drug entrapment efficiency (88.02 ± 1.21%). Mupirocin (MC) loaded NLC based gel demonstrated sustained drug profile with significant increase (P < 0.05) in drug deposition in skin (about 26%) with non-irritant properties to the skin. Stability study showed no significant changes of the parameters during and after the study. In conclusion, developed Mupirocin (MC) loaded NLC based gel could serve as a novel approach in treatment of impetigo by deliver the drug topically with sustained effect and improved patient compliance.

Severe Systemic Allergic Reaction after Topical Application of Mupirocin

Mupirocin (MUP) is a natural derivative of crotonic acid extracted from Pseudomonas fluorescens. This antibiotic has a unique chemical structure and mechanism of action.It is often used topically for the treatment of cutaneous infections to prevent skin and soft tissue infections caused by S. aureus isolates and where the MRSA isolates are epidemic. Furthermore, MUP may be used as a choice drug for nasal decolonization.Despite some side effects, mupiro¬cin has been reported to be safe and to cause allergic reactions in only extremely rare cases. This paper is a report on a rare case of severe systemic allergic reaction resulting from treatment with mupirocin ointment in a 39 year old male patient who had a history of burn injury.

Analytical Method Development and Validation for Simultaneous Determination of Simvastatin and Mupirocin Using Reverse-Phase High-pressure Liquid Chromatographic Method

This study was aimed to develop and validate the use of reverse-phase high pressure liquid chromatographic method for the estimation of simvastatin (SIM) and mupirocin (MUP) simultaneously. The chromatographic method developed is optimized for flow rate with the column, solvent, and buffer used and mobile phase ratio, molarity, and pH. The validation of the optimized method and the forced degradation studies of both drugs (under acidic, alkaline, oxidation, heat, light, and neutral conditions) were conducted following the The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. Kromasil C18 column (250 mm × 4.6 mm, 5 µm) with ultraviolet detection at 224 nm and acetonitrile/phosphate buffer (30 mM, 70:30 v/v, pH 3.5; adjustment done using orthophosphoric acid) as mobile phase at a flow rate of 1.1 mL/min were observed to provide a good resolution for MUP and SIM at retention times of 2.32±0.008 and 13.55±0.254 min, respectively, with high accuracy (percent recovery was 99.69±0.82 for MUP and 101.10±0.02 for SIM) and linearity in the range of 5-30 µg/mL (r2: 0.9969 for MUP and r2: 0.9959 for SIM). The diagnostic limit and the lower limit of determination were 0.771±0.234 and 2.338±0.246 μg/mL for MUP and 0.595±0.282 and 1.803±0.334 µg/mL for SIM, respectively. The validated method was used to understand the degradation behavior of both drugs after the forced degradation studies. The analytical method developed is determined to be specific, sensitive, precise, and accurate for the estimation of MUP and SIM simultaneously in the combined dosage form.

Effect of mupirocin in Helicobacter pylori in vitro

Mupirocin (MUP) is an effective antibiotic against MRSA. Its bactericidal effect is stable under acid condition. By validating its antibacterial effect of Helicobacter pylori, we try to clarify MUP effect on H. pylori. The present study was conducted to investigate the effect of MUP on clarithromycin (CLR) / metronidazole (MNZ) -resistant and -susceptible strains of H. pylori, the time-kill effect of MUP, and the post antibiotic effect (PAE). We investigated the minimal inhibitory concentration (MIC) and the minimal bactericidal effect (MBC) of MUP against 140 H. pylori, which include clinical strains, ATCC43504, 26695 and J99. Ten of them were CLR -resistant strains and 3 were MNZ-resistant strains. The MIC90 and MBC of MUP on all 140 strains is 0.064 μg / ml, and 0.1 μg / ml, respectively. There were no differences of MUP effect between susceptible and resistant strains either for CLR or MNZ. Time-kill curve test and PAE test of MUP on ATCC43504 were performed. By adding MUP, time-kill curve showed that bacterial quantities decreased in dose and time-dependent manner. No viable colony was found after 12-hour culture with 0.1 μg / ml MUP. The value of PAE is 12. MUP is a potential effective antibiotic for H. pylori even those for CLR / MNZ -resistant strains.

Comparative Performances of Vitek-2, Disk Diffusion, and Broth Microdilution for Antimicrobial Susceptibility Testing of Canine Staphylococcus pseudintermedius.

Staphylococcus pseudintermedius is the primary cause of canine cutaneous infections and is sporadically isolated as a pathogen from humans. Rapidly emerging antibiotic-resistant strains are creating serious health concerns so that accurate and timely antimicrobial susceptibility testing (AST) is crucial for patient care. Here, the performances of the AST methods Vitek-2, disk diffusion (DD) and broth microdilution (BMD) were compared for the determination of susceptibility of 79 S. pseudintermedius isolates from canine cutaneous infections and one from human pyoderma to oxacillin (OXA), amoxicillin/clavulanate (AMC), cephalothin (CEF), gentamicin (GEN), enrofloxacin (ENR), doxycycline (DOX), clindamycin (CLI), inducible clindamycin resistance (ICR), mupirocin (MUP), and trimethoprim-sulfamethoxazole (SXT). Overall, the agreement of DD and Vitek-2 using the veterinary AST-GP80 card with reference BMD was ≥90%, suggesting reliable AST performances. While DD generated mainly minor errors and one major error for OXA, Vitek-2 produced one very major error for GEN, and it failed in identifying one ICR-positive isolate. Moreover, five bacteria were diagnosed as ICR-positive by Vitek-2, but they showed a noninduction resistance phenotype with manual methods. All S. pseudintermedius isolates were interpreted as susceptible or intermediately susceptible to DOX using CLSI breakpoints for human staphylococci that match the DOX concentration range included in AST-GP80. However, this could lead to inappropriate antimicrobial prescription for S. pseudintermedius infections in companion animals. Considering the clinical and epidemiological importance of S. pseudintermedius, we encourage updating action by the system manufacturer to address AST for this bacterium.

Application of reactive extraction for the separation of pseudomonic acids: Influencing factors, interfacial mechanism, and process modelling

AbstractMupirocin (a mixture of A, B, C, and D pseudomonic acids—four complex, similar structures) is an antibiotic belonging to the monocarboxylic acid class, used to cure infections caused by bacteria (Gram‐positive), especially methicillin‐resistant Staphylococcus aureus (MRSA). Its biotechnological production and separation need constant attention, as improving antibiotics is important in the pharmaceutical industry. This is the first study regarding pseudomonic acids separation through reactive extraction; the experiments were focused on finding a proper combination of extractant and diluent for optimization of the separation yield. The pH influence (4–9) and extractant (TOA and Amberlite LA‐2, 5–20 g/L) concentration dissolved in n‐heptane (green solvent) have been analyzed, obtaining the maximum extraction yield (88.78%) at pH 4, 20 g/L extractant, and 10% octanol added to the organic solvent. The addition of the phase modifier, 1‐octanol, improved the extraction yield by 2.6 times for Pseudomonic acid A due to interactions of formed complexes with the phase modifier that improves its solubility. The experimental results for determining the mechanism of the interfacial reaction showed that, regardless of the pH value and solvent polarity (modified by the addition of 1‐octanol), only one molecule of Pseudomonic acid A and extractant react at the aqueous‐organic interface. In addition, the system was modelled and optimized with a methodology combining artificial neural networks (ANN) and differential evolution.

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.

Assessment of Mupirocin Resistance among Clinical Isolates of Methicillin Resistant Staphylococcus aureus

Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is considered a major risk factor for nosocomial infections and its decolonization has reduced these infections. Mupirocin (MUP) is the topical antibiotic of choice for decolonization. MUP decolonization failure is attributed to MUP resistance. Objective: The aim of the current study is to assess MUP resistance among MRSA isolates phenotypically and genotypically. Methodology: Fifty MRSA isolates were identified in Microbiology Department in the Medical Research Institute hospital, Alexandria University. Antibiotic susceptibility to different classes of antibiotics by disk diffusion method was done. MUP minimum inhibitory concentration (MIC) was determined phenotypically by MUP Ezy MIC™ Strips. MUP resistance was determined genetically by multiplex PCR detection of mupA and mupB. Results: Of all MRSA isolates, 6% exhibited high level and none showed low level MUP resistance. Only mupA was detected in all resistant isolates. Conclusion: Despite low prevalence of MUP resistance, it is appropriate to test MUP resistance prior nasal decolonization

Do Antimicrobial Resistance Patterns Matter? An Algorithm for the Treatment of Patients With Impetigo

Background Impetigo, a highly contagious bacterial skin infection commonly occurring in young children, but adults may also be affected. The superficial skin infection is mainly caused by Staphylococcus aureus (S. aureus) and less frequently by Streptococcus pyogenes (S. pyogenes). Antimicrobial resistance has become a worldwide concern and needs to be addressed when selecting treatment for impetigo patients. An evidence-based impetigo treatment algorithm was developed to address the treatment of impetigo for pediatric and adult populations. Methods An international panel of pediatric dermatologists, dermatologists, pediatricians, and pediatric infectious disease specialists employed a modified Delphi technique to develop the impetigo treatment algorithm. Treatment recommendations were evidence-based, taking into account antimicrobial stewardship and the increasing resistance to oral and topical antibiotics. Results The algorithm includes education and prevention of impetigo, diagnosis and classification, treatment measures, and follow-up and distinguishes between localized and widespread or epidemic outbreaks of impetigo. The panel adopted the definition of localized impetigo of fewer than ten lesions and smaller than 36 cm2 area affected in patients of two months and up with no compromised immune status. Resistance to oral and topical antibiotics prescribed for the treatment of impetigo such as mupirocin, retapamulin, fusidic acid, have been widely reported. Conclusions When prescribing antibiotics, it is essential to know the local trends in antibiotic resistance. Ozenoxacin cream 1% is highly effective against S. pyogenes and S. aureus, including methycyllin-susceptible and resistant strains (MRSA), and may be a suitable option for localized impetigo.J Drugs Dermatol. 2021;20(2):134-142. doi:10.36849/JDD.2021.5475 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Film Forming, Antimicrobial and Growth Promoting Wound Healing Spray Formulation

Background: Bacterial infections at wound site are one of the major causes for delayed healing. The aim of this study was to develop topical film forming spray having Combination of Simvastatin and Mupirocin which can avoid such infections and provide enhanced wound healing. Methods: Film forming spray formulation having Simvastatin and Mupirocin was formulated using Eudragit E100as film forming agent and Glycerol and Polyethylene glycol (PEG-400) as plasticizers. The effect of these excipients on the formulation was assessed by applying factorial design. Optimized formulation was evaluated for swelling index, spray angle, spray pattern, invitro drug release, evaporation time, average weight per dose, antimicrobial efficacy and in-vivo wound healing was assessed and compared with marketed formulation by excision wound healing model. Results: The optimized batch of topical film forming spray having combination of Simvastatin and Mupirocin was selected based on the results of swelling index and in-vitro drug release at respective drugs. Both the drugs gave more than 80% of drug release within 2 hrs and showed satisfactory physicochemical and mechanical properties along with potent antimicrobial efficacy against S. aureus and E. coli. Developed formulation showed comparative wound healing activity as that of marketed conventional formulation. Conclusion: Topical film forming spray was successfully developed using combination of Simvastatin and Mupirocin Calcium. Antimicrobial activity and results of animal studies indicated safety and efficacy of formulation.

Impact of formulary interventions on the minimum inhibitory concentration of methicillin-resistant Staphylococcus aureus to mupirocin, chlorhexidine, and octenidine in a Singapore tertiary institution.

Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is an effective measure to prevent clinical infection but resistance is a concern. We aim to evaluate the impact of mupirocin (MUP) ointment formulary removal, plateauing use of chlorhexidine gluconate (CHG), and hospital-wide introduction of octenidine (OCT)-based products on the minimum inhibitory concentration (MIC) of MRSA to MUP, CHG, and OCT in our hospital. A prevalence study was conducted at three time points (TP) on consecutive MRSA screening isolates to evaluate for their MICs to MUP, CHG, and OCT using broth microdilution sensititre plates and detection of the ileS-2 gene encoding high-level MUP resistance in 2013 (pre-intervention TP1; n = 160), 2016 (early post-intervention TP2; n = 99) and 2017 (late post-intervention TP3; n = 76). Statistical analyses were performed using Chi square test with reference from TP1. There was a significant improvement in MUP susceptibility (MIC < 4 mcg/ml) from 71.9% (TP1) to 86.9% (TP2; p = 0.006) to 88.2% (TP3; p = 0.007). The prevalence of MUP high-level resistance (MIC > 256 mcg/ml) reduced from 25.0% (TP1) to 12.1% (TP2; p = 0.014) to 5.3% (TP3; p = 0.001). Likewise, the prevalence of isolates harboring the ileS-2 gene decreased from 28.1% (TP1) to 18.2% (TP2; p = 0.072) to 9.2% (TP3; p = 0.002). OCT MIC range remains stable at 0.5 to 1 mcg/ml across all three TPs. The proportion of isolates with reduced CHG susceptibility (MIC ≥ 4 mcg/ml) increased over the three TPs from 23.1 to 27.2% (p = 0.45) to 42.1% (p = 0.003). Active formulary regulations have an impact on the resistance profile of MRSA and can be used as a strategy to preserve the MRSA decolonization armamentarium.