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.
SSTIs | Infection | Pathogen | Description | Ref. | |||||||||||||||
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Non-purulent SSTIs | Impetigo | Staphylococcus aureus, Streptococcus pyogenes | Superficial infection developed via direct or indirect invasion of bacteria. It is the most common infection in children and presents in two forms, i.e., bullous and non-bullous impetigo. | [7][9][13] | [7,9,13] | ||||||||||||||
Cellulitis | Staphylococcus aureus, | beta-hemolytic streptococci (groups A, B, C, or G) | Subcutaneous infections are accompanied by lymphadenopathy and lymphangitis. It is characterized by redness, edema, or induration and usually affects lower limbs. | [7] | |||||||||||||||
Erysipelas | Staphylococcus aureus, Streptococcus pyogenes | Superficial lymphatics and upper dermis infection, usually affects the face and sometimes lower limbs. It possesses well-defined sharp raised borders in contrast to non-infected areas. | [7][13] | [7,13] | |||||||||||||||
Folliculitis | Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes | It is a superficial inflammation of hair follicles, mainly affecting moist skin with hair. | [7][9][14] | [7,9,14] | |||||||||||||||
Purulent SSTIs | Furuncle | Staphylococcus aureus | Furuncle or boil is a deep inflammatory infection developed from folliculitis. Initially, it is a firm, tender, erythematous nodule that becomes fluctuant and painful. It usually infects the face, buttocks, and axillae. | [9][13] | [9,13] | ||||||||||||||
Carbuncle | Staphylococcus aureus, Streptococcus pyogenes | It is an aggregation of multiple furuncles, involves infection of the hair follicle, and is further extended to subcutaneous tissues. The infection is painful and tender but the patient is well. It is usually observed at the neck, back, and thighs. | [7][ | Surgical wound | Staphylococcus aureus | Chitosan | 9][13] | [7,9,13] | |||||||||||
The formulated spherical membrane exhibited superior adhesion and elasticity along with progressive drug release. The Draize patch test revealed that the developed membrane was non-irritant to the skin, along with having magnified antimicrobial efficiency and enhanced retention to the skin. | [ | 33 | ] | [44] | Abscess | Staphylococcus aureus, Streptococcus pyogenes, | Streptococcus milleri, viridans, streptococci, coagulase–staphylococci | Focal collection of pus in dermis and hypodermis, characterized by tender, red nodules surrounded by erythematous swelling. | [7][9][15 | ||||||||||
Skin injuries | Acrylic acid | ][16] | [7,9,15,16] | ||||||||||||||||
The developed patches exhibited good elasticity and tensile strength, along with enhanced permeation and retention into the skin. The patches were non-irritant to the skin, evidenced by the Draize patch test. | [ | 34 | ] | [45] | Complex SSTIs | Burn wound | Anaerobes | Burn wound infection possesses a high bacteria concentration (>10 | |||||||||||
Liposomes | Methicillin-resistant | Staphylococcus aureus | (MRSA), | Staphylococcus aureus5 | colonies forming unit). It arises immediately after the injury due to the damage of the cutaneous barrier and adaptive immunity. The surrounding tissues of the burn wound exhibit warmth, tenderness, induration, and erythema. | [6][17] | [6,17] | ||||||||||||
Hydrogenated soy phosphatidylcholine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- | [methoxy (PEG)-2000], cholesterol | Mupirocin was administered intravenously the first time with a distinctive mechanism of action that resulted in a better approach for the treatment of resistant bacterial infection. Further, the results stipulated that nano-mupirocin extended the topical application of mupirocin to the systemic application for the treatment of MRSA infections by changing the pharmacodynamics of mupirocin. | [ | 35][36][37] | [46,47,48] | Surgical site infection | Escherichia coli | It usually arises 4 days after surgery and is categorized into superficial incisional, deep incisional, and organ or space infection. It is diagnosed by incisional discharge, swelling, tenderness, and erythema. | [18] | ||||||||||
Liposomal hydrogel | Burn therapy | Staphylococcus aureus | and | Bacillus subtilis | Chitosan | Mupirocin-loaded liposomal hydrogel system exhibited prolonged release and superior bio-adhesiveness in contrast to the marketed formulation of mupirocin. In vitro and in vivo studies stipulated that the developed system was significantly safe, more therapeutically active along with shorter healing time, and exhibited antibiofilm activity against the bacterial pathogen. | [38][39] | [49,50] | Diabetic foot infection | Staphylococcus aureus, | Enterococci, | Pseudomonas aeruginosa, Enterobacteriaceae, Acinetobacter | spp., | Bacteroides | spp. | This infection is most common in diabetic patients and possesses high mortality. This infection encompasses a range from nails to necrotizing limbs. Nails serve as an entry portal for bacterial infection due to poor hygiene. | [6][19][20] | [6,19, | |
Microparticles/Microspheres | 20 | ] | |||||||||||||||||
Wound healing | Staphylococcus aureus | Eudragit | The developed formulation exhibited the sustained release of mupirocin along with magnified storage. The morphology, drug release, and antimicrobial activity of the developed formulation were dependent on the drug loading and the solvent. Time-kill assay results revealed that there was no loss of the antimicrobial activity of mupirocin during the encapsulation. | [ | 40][41] | [51,52] | Necrotizing SSTIs | Monomicrobial, Polymicrobial | Staphylococcus aureus, Streptococcus pyogenes | Gram-negatives, | Clostridium | species, Anaerobic bacteria | Necrosis of soft tissues or muscles is initially characterized by erythema and induration with pain followed by skin color change to blue/purple. The patient suffers from systemic toxicity, multi-organ failure, and hemodynamic instability. | [6][7][9] | [6,7,9] | ||||
Bite wounds | Human and animal bite | Eikenella corrodens, Pasteurella multocida, Pasteurella canis, Capnocytophaga canimorsus, | Staphylococcus aureus | It usually arises after biting. | [7][21][22] | [7,21,22] |
Drug Delivery System | Infection | Pathogen | Biomaterial | Outcome | Ref. | |||||||||||||
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Composite biomaterials/scaffold | Wound healing | Staphylococcus aureus, Bacillus subtilis, Escherichia coli | Collagen, Silica | The collagen scaffolds exhibited more therapeutic potential for the treatment of wound infection and displayed a promising carrier approach for tissue engineering. | [28] | [39] | ||||||||||||
The developed bio-composite exhibited enhanced water uptake, sustained release, and antimicrobial activity. In vivo results stipulated that the biomaterial showed enhanced adhesion and wound contraction rate, supported by histopathological analysis. | [29] | [40] | ||||||||||||||||
Hydrogel dressings | Wound healing | Escherichia coli | (ATCC 8739), | Enterococcus hirae | (ATCC 10541), | S. aureus | (ATCC 6538), | Pseudomonas aeruginosa | (ATCC 27853), | Bacillus | cereus | (ATCC 7064) | , Klebsiella pneumonia | Chitosan, sodium alginate, carbopol | The developed composite film accelerated the regeneration of the epidermal layer in contrast to the marketed commercial formulation. | [30] | [41] | |
Diabetic wound | Polyvinyl alcohol | The developed gel was effective for the treatment of diabetic wound and accelerated the wound closure. | [31] | [42] | ||||||||||||||
Primary and secondary | Gram-positive and Gram-negative bacteria | Chitosan | The prepared polymeric membrane was spherical, stable, and elastic, along with having the controlled release property. Furthermore, the membrane exhibited magnified retention of the drug in the skin without any irritation. | [32] | [43] | |||||||||||||
Microsponges | ||||||||||||||||||
Surgical wound | ||||||||||||||||||
Staphylococcus aureus | Ethylcellulose | Mupirocin microsponge exhibited a diffusion-controlled release profile along with ~5 times magnified retention on rat skin in contrast to the marketed formulation. The formulation was found stable and non-irritant, evidenced by the Draize patch test. | [ | 42 | ] | [53] | ||||||||||||
Wound healing | Staphylococcus aureus, Escherichia coli | Keratin, fibrin, and gelatin | The developed formulation exhibited a prolonged release pattern along with enhanced biocompatibility and cell adhesion properties. The antimicrobial activity results demonstrated that the mupirocin-loaded sponge was a promising medicated dressing material for the treatment of wound infection. | [43] | [54] | |||||||||||||
Nanocapsule/nanoparticles | Wound healing | Poly(ε-caprolactone) | The developed nanocapsules showed excellent stability at 40 °C and room temperature. | [44] | [55] | |||||||||||||
Methicillin-resistant | Staphylococcus aureus | (MRSA) | Chitosan, selenium | The tailored formulation showed remarkable therapeutic potential in terms of diabetic wound healing and wound contraction compared to the native mupirocin. | [45] | [56] | ||||||||||||
Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, | and | Escherichia coli | Poly(ethylene oxide)–poly (propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) | The tailored formulation exhibited reduced minimum inhibitory concentrations and minimum bactericidal concentrations against | S. aureus, S. epidermidis, Pseudomonas aeruginosa, | and | E. coli | compared to the mupirocin ointment. Further, the developed formulation was safe, effective, and biocompatible for the treatment of wound infection. | [46][47] | [57,58] | ||||||||
Nanofibers | Wound healing | Staphylococcus aureus | Poly-l-lactic acid | The tailored scaffold exhibited a different release profile for both drugs, suggesting that the release kinetics of one drug was altered by keeping the two different drugs in the same polymer matrix. The dual drug scaffold released a significantly higher drug and even compensated the inactive monic acid to act on the applied area, resulting in the maintainence of a sufficient concentration of mupirocin in the infected wound for more than a 72 h period, resulting in profound wound healing. | [48] | [59] | ||||||||||||
Burn wound | Staphylococcus aureus, Pseudomonas aeruginosa, | and | Escherichia coli | Polyurethane | The developed fiber mat was enough for wound hydration via providing adequate environmental humidity. Moreover, the tailored nanofiber exhibited sufficient cell spreading and attachment. The cytotoxicity results revealed that the antibacterial activity of the scaffold was increased proportionally with the increase in mupirocin concentration (2–5%). Further, the histopathological study revealed that the nanofibrous mat was enough for burn wound healing due to negligible inflammation. | [49] | [60] | |||||||||||
Staphylococcus aureus, Pseudomonas aeruginosa, | and | Escherichia coli | Polycaprolactone | The tailored multifunctional double-layer nanofibrous scaffold (MDLS) was effective for the management of wound infection, along with superior tensile strength with enhanced contact angle and swelling ratio. Furthermore, cytotoxicity results revealed that the MDLS was more biocompatible due to the addition of chitosan in contrast to polycaprolactone nanofibers. | [50] | [61] | ||||||||||||
Staphylococcus aureus, | and | Escherichia coli | Keratin, and coenzyme Q10, and polyvinyl alcohol | The tailored formulations were biocompatible, evidenced by the skin irritancy test. Further, the therapeutic efficacy of the tailored formulation was assessed by antimicrobial activity against various strains of | S. aureus | (2583, 2586, 2587, 2590), MRSA 2555, and | E. coli | 1808. Moreover, cell proliferation results evidenced the ability of nanofibers to support the keratinocytes’ growth due to the presence of coenzyme Q10. | [51] | [62] | ||||||||
Topical spray | Burn wound | Staphylococcus aureus, Pseudomonas aeruginosa, | and | Escherichia coli, | and | Streptococcus suis (S. suis) | Eudragit E100 | The developed spray exhibited magnified antimicrobial activity (18-fold) against | S. suis | , in contrast to the marketed formulation due to close contact between spray and skin, leading to the formation of a thin film on the infected surface. Moreover, the topical formulation was found non-irritant to the human skin without any toxicity to the monocytes, keratinocytes, and fibroblasts cells. Additionally, the safety profile of the formulation was also confirmed by zero production of nitric oxide and inflammatory cytokines (IL-1b and TNF-a) due to its antiendotoxin effect. | [18][52] | [18,63] | ||||||
Nanostructured lipid carrier | Cetyl palmitate, caprylic acid | Nanostructured lipid carrier (NLC) reduced the metabolic degradation of MUP via the protective lipid layer of NLC which resulted in a 40-fold and 55-fold area under the curve and half-life, respectively, in contrast to native MUP. | [53] | [64] |