Topical Antimicrobials Research Articles

Interventions in infected venous leg ulceration in clinical practice

Annemarie Brown explores the vital role practice nurses play in caring for patients with infected venous leg ulcers. In particular, recognising signs and symptoms, management, and the threat of antimicrobial resistance will be discussed This article aims to inform practice nurses of the management of infection in venous leg ulcers which they may encounter in clinical practice. It outlines the infection continuum, how to recognise the signs and symptoms of an increasing bacterial burden and how this can be effectively managed to prevent the patient developing a systemic infection. In view of Government policies to reduce the inappropriate use of systemic antibiotics, guidance on using topical antiseptics and antimicrobials is discussed, together with information on the various products available. The signs of sepsis are discussed to ensure that readers are familiar with this life-threatening condition.

Protocol for a randomized clinical trial exploring the effect of antimicrobial agents on the penile microbiota, immunology and HIV susceptibility of Ugandan men

BackgroundThe foreskin is the main site of HIV acquisition in a heterosexual uncircumcised man, but many men in endemic countries are reluctant to undergo penile circumcision (PC). Observational studies suggest that proinflammatory anaerobic bacteria are enriched on the uncircumcised penis, where they may enhance HIV susceptibility through increased foreskin inflammatory cytokines and the recruitment of HIV-susceptible CD4+ target cells. This trial will examine the impact of systemic and topical antimicrobials on ex vivo foreskin HIV susceptibility.Methods/designThis randomized, open-label clinical trial will randomize 125 HIV-negative Ugandan men requesting voluntary PC to one of five arms (n = 25 each). The control group will receive immediate PC, while the four intervention groups will defer PC for 1 month and be provided in the interim with either oral tinidazole, penile topical metronidazole, topical clindamycin, or topical hydrogen peroxide. The impact of these interventions on HIV entry into foreskin-derived CD4+ T cells will be quantified ex vivo at the time of PC using a clade A, R5 tropic HIV pseudovirus assay (primary endpoint); secondary endpoints include the impact of antimicrobials on immune parameters and the microbiota of the participant’s penis and of the vagina of their female partner (if applicable), assessed by multiplex enzyme-linked immunosorbent assay and 16S rRNA sequencing.DiscussionThere is a critical need to develop acceptable, simple, and effective means of HIV prevention in men unwilling to undergo PC. This trial will provide insight into the causative role of the foreskin microbiota on HIV susceptibility, and the impact of simple microbiota-focused clinical interventions. This may pave the way for future clinical trials using low-cost, nonsurgical intervention(s) to reduce HIV risk in uncircumcised heterosexual men.Trial registrationClinicalTrials.gov, NCT03412071. Retrospectively registered on 26 January 2018.

Chlorquinaldol, a topical agent for skin and wound infections: anti-biofilm activity and biofilm-related antimicrobial cross-resistance.

PurposePersistence of skin and wound infections is nowadays accepted being linked to bacterial biofilms, which are highly recalcitrant to treatments and contribute to maintain a constant inflammation state and prevent a correct healing. Topical antimicrobials are the most common first-line self-medications; however, treatment failure is not uncommon and emerging resistance to antibiotics is alarming. Chlorquinaldol is an antimicrobial with a wide spectrum of activity and desirable characteristics for topical application. Aim of this study was to evaluate the efficacy of chlorquinaldol to prevent or eradicate S. aureus and P. aeruginosa biofilms, in comparison to classic topical antibiotics like gentamicin and fusidic acid.MethodsMinimum inhibitory concentrations (MIC) were assessed for each strain and subinhibitory concentrations (½ and ¼ MIC) were used in the biofilm assay. Antimicrobial assays were performed during biofilm formation or were applied on mature biofilms and were evaluated by means of crystal violet assay and confocal laser scan microscopy.ResultsChlorquinaldol and gentamicin were the most effective antimicrobials in both eradicating and preventing pathogens biofilm; however, resistance to methicillin and impermeability to carbapenems impaired chlorquinaldol effect. In addition, similarly to other hydroxyquinolines, aspecific metal chelation is here proposed as chlorquinaldol mode of action.ConclusionRelying on an acceptable antibiofilm and a wide spectrum of activity, an aspecific mode of action and consequent absence of resistance development, chlorquinaldol proved to be a good antimicrobial for topical use.

Relationship between quinolone use and resistance of Staphylococcus epidermidis in patients with acne vulgaris.

Staphylococcus epidermidis is a bacterium known to inhabit the skin. In treatment of acne vulgaris, the cutaneous milieu is exposed to oral or topical antimicrobials. We previously reported that the antimicrobial resistance of Cutibacterium acnes isolated from acne patients is affected by antimicrobial use. The aim of this study was to investigate the relationship between quinolone use and resistance in skin bacteria, particularly S.epidermidis, from acne patients. A total of 92 and 87 S.epidermidis strains isolated from clinic patients and hospital outpatients with acne vulgaris, respectively, were tested. No significant difference was found between the prevalence of methicillin-resistant S.epidermidis (MRSE) strains from clinic patients (37.0%) and hospital outpatients (39.1%). The MRSE strains (20.6%, 14/68 strains) showed a significantly higher ratio of high-level levofloxacin resistance (minimum inhibitory concentrations were 64 to ≥256μg/mL) compared with methicillin-susceptible S.epidermidis strains (2.7%, 3/111 strains) (P<0.01). The rate of levofloxacin resistance in C.acnes strains, which were isolated from the same samples of acne patients, showed a strong positive correlation with that in S.epidermidis strains (r=0.93, P<0.01). The high-level levofloxacin-resistant strains were frequently found in patients with history of quinolone use compared with those without (P<0.01). Our data showed for the first time that antimicrobial administration for acne treatment affects the antimicrobial resistance in not only C.acnes but also S.epidermidis. Thus, caution should be exercised in antimicrobial use for acne treatment to prevent increasing antimicrobial resistance in these species.

“Smart” polymer enhances the efficacy of topical antimicrobial agents

The delivery of antimicrobial agents to surface wounds has been shown to be of central importance to the wound healing process. In this work, we prepared film forming wound care formulations containing 3 polymers (FTP) that provide broad-spectrum antimicrobial protection for prolonged periods. FTP formulations comprises of a smart gel matrix comprising of pH-degradable and temperature responsive polyacetals (smart polymer) which allow for the FTP films to be hydrophobic at room temperature, preventing accidental rubbing off, and hydrophilic at lower temperatures, allowing for easy removal. Two FTP smart-antimicrobial films were evaluated in this work: FTP-AgSD (Silver sulfadiazine actives), and FTP-NP (Neosporin actives). The in vitro and ex vivo antimicrobial efficacy studies show that FTP-AgSD films are significantly more effective for longer durations against Staphylococcus aureus (3 days), Candida albicans (9 days) and Pseudomonas aeruginosa (4 days) when compared to the cream formulations containing antimicrobials. FTP-NP films showed significantly improved antimicrobial activity for a minimum of 3 days for all pathogens tested. Moreover, when tested ex vivo in porcine skin, FTP-AgSD and FTP-NP showed average improvements of 0.89 log10 and 1.66 log10 respectively over standard cream counterparts. Dermal toxicity studies were carried out in a rat skin excision model which showed a similar wound healing pattern to that in rats treated with standard cream formulations as represented by reduction in wound size, and increase in wound healing markers.

Can pyoderma in dogs be treated with fewer antibiotics?

Staphylococcal skin infections, generally referred to as pyoderma, are a very common reason for the prescription of antimicrobials for pet dogs.1-3 These infections, usually involving Staphylococcus pseudintermedius , vary in...

Антимикробные препараты местного действия для профилактики инфекционных осложнений интравитреальных инъекций

Антимикробные препараты местного действия для профилактики инфекционных осложнений интравитреальных инъекций

Chronic pododermatitis and interdigital furunculosis in dogs

Chronic pododermatitis with interdigital furunculosis is a common and frustrating problem in dogs. It is characterised by the presence of recurrent interdigital furunculosis. It is a multifactorial condition with primary, predisposing and perpetuating causes that lead to the secondary infections. Almost any skin disease can trigger the initial inflammation, but atopic dermatitis, adverse food reactions and abnormal conformation are the most common. Predisposing factors such as short hairs, excess weight, and altered weight bearing may lead to the development of the interdigital furunculosis. Perpetuating changes prevent resolution; these include weight bearing on haired skin, conjoined pads, new pad formation, deep tissue pockets, ingrown hairs and sinus tracts. All of the contributing factors in each case must be identified and managed. Supportive care includes analgesia, weight loss, using boots, keeping the interdigital skin clean, and using lubricating creams. Secondary bacterial and/or Malassezia spp. infections should be managed with appropriate topical and/or systemic antimicrobials. Bacterial infections can be deep, mixed and/or antimicrobial resistant, and culture and antimicrobial susceptibility testing must be used to select effective drugs. Chronic inflammatory changes can be managed with topical or systemic glucocorticoids, topical 0.1% tacrolimus, ciclosporin or cytotoxic drugs. Chronic proliferative changes are poorly responsive to medical management alone, therefore surgical fusion or laser podoplasties should be considered. Long-term treatment of the primary, predisposing and perpetuating problems is required to maintain remission and prevent recurrence.

Prevention Strategies for Recurrent Community-Associated Staphylococcus aureus Skin and Soft Tissue Infections.

Staphylococcus aureus skin and soft tissue infections (SSTI) are a major source of morbidity. More than half of patients experiencing SSTI will have at least one recurrent infection. These infections frequently cluster in households. Given the burden these infections pose to patients and healthcare, prevention strategies are of major clinical importance and represent an active area of research. Bacterial colonization is frequently an early and critical step in the pathogenesis of infection. As such, strategies to prevent reinfection have aimed to decrease staphylococcal colonization of the skin and mucus membranes, a process referred to as decolonization. Treatment of acute SSTI with incision and drainage and systemic antibiotics is the mainstay of therapy for healing of the acute infection. Systemic antibiotics also provide benefit through reduced incidence of recurrent SSTI. Education for patients and families regarding optimization of personal and household hygiene measures, and avoidance of sharing personal hygiene items, is an essential component in prevention efforts. For patients experiencing recurrent SSTI, or in households in which multiple members have experienced SSTI, decolonization should be recommended for all household members. A recommended decolonization regimen includes application of intranasal mupirocin and antiseptic body washes with chlorhexidine or dilute bleach water baths. For patients who continue to experience recurrent SSTI, periodic decolonization should be considered. Personal decolonization with topical antimicrobials and antiseptics reduces the incidence of recurrent S. aureus SSTI. Future avenues for investigation include strategies for household environmental decontamination as well as manipulation of the host microbiota.

Approaches to the treatment of bacterial infections of the respiratory tract based on current data of the microbiome

Respiratory infections are mainly caused by viruses or bacteria that often interact. In the upper respiratory tract there is a wide range of commensals and potential pathogenic bacteria that, together with other bacteria, viruses and fungi, form complex ecological networks known collectively as “the microbiome”. It is assumed that this community is constantly exposed to synergistic and competitive interspecific interactions. The microbiome of the respiratory tract is a factor of respiratory health, which changes (respiratory viral infections, inappropriate use of antibiotics) can lead to bacterial complications and the spread of respiratory tract infections in. In the light of current guidelines for limiting the use of systemic antibiotics in case of uncomplicated acute respiratory tract infections, a real alternative is the use of topical antimicrobial agents, for example, thiamphenicol glycinate acetylcysteinate. The article presents the results of the use of the drug in respiratory infections of the upper and lower respiratory tract.

Interface infectious keratitis after anterior and posterior lamellar keratoplasty. Clinical features and treatment strategies. A review

Interface infectious keratitis (IIK) is a novel corneal infection that may develop after any type of lamellar keratoplasty. Onset of infection occurs in the virtual space between the graft and...

In vitro antimicrobial activity of topical otological antimicrobials and Tris-EDTA against resistant Staphylococcus pseudintermedius and Pseudomonas aeruginosa isolates from dogs.

The value of susceptibility tests for the selection of topical otological antimicrobial agents is unclear. Laboratories test antibiotic concentrations substantially lower than concentrations supplied in topical formulations. Additionally, microbiological consensus statements are not available for topical antimicrobials. The primary aim of this study was to measure the minimum inhibitory and bactericidal concentrations of enrofloxacin, gentamicin, marbofloxacin, neomycin, orbifloxacin, polymyxin B and silver sulfadiazine from concentrations available in otological formulations (COF) to 1:59,000 dilution. The secondary aim was to evaluate the effect of Tris-EDTA in conjunction with these antimicrobial agents. Twenty resistant clinical isolates [Staphylococcus pseudintermedius (n = 10) and Pseudomonas aeruginosa (n = 10)] were tested by broth microdilution using a concentrated inoculum (3.75 × 107 cfu/mL). Concentrations available in otological formulations were at least 26× greater than the MICs for S. pseudintermedius and P. aeruginosa. COFs of polymyxin B and SSD were 27× greater than the MBCs for P. aeruginosa, whereas all other antimicrobial COFs were equal to or less than the MBCs for both organisms. Tris-EDTA significantly reduced the MICs of all antimicrobials, except with SSD for P. aeruginosa, and it significantly increased the MIC of SSD for S. pseudintermedius. Further studies are warranted to validate the present results in vivo. COFs are inhibitory and less likely bactericidal, with few exceptions, against resistant strains of these organisms. Tris-EDTA may be advantageous for P. aeruginosa whereas no additional benefit is afforded against S. pseudintermedius. Susceptibility tests may not be useful for the selection of topical otological antimicrobial agents.

Determination of minimum inhibitory concentrations for silver sulfadiazine and other topical antimicrobial agents against strains of Pseudomonas aeruginosa isolated from canine otitis externa.

Otitis externa is a common presenting complaint in practice. Ear infections by Pseudomonas aeruginosa are particularly problematic due to the organism's high level of resistance and ability to damage the tympanum. Treatment should be based on susceptibility testing although minimum inhibitory concentrations (MICs) are not available for all treatment options. Silver sulfadiazine has been used in cases of recurrent P.aeruginosa otitis, although a MIC for silver sulfadiazine as a single agent has not been established. To describe susceptibility patterns of P.aeruginosa isolated from canine otitis externa and determine the MIC for silver sulfadiazine and other topical antimicrobials. Thirty-six P.aeruginosa isolates were collected from client-owned dogs, suffering from otitis externa. Susceptibility patterns were established using disc diffusion susceptibility testing against 17 antimicrobial agents. For determination of the MIC, selected strains were tested against increasing concentrations of marbofloxacin, enrofloxacin, gentamicin, polymyxin B and silver sulfadiazine using broth microdilution. For nine of 17 antimicrobial agents, complete resistance was seen in all isolates tested via disk diffusion susceptibility testing. Approximately 94% and 96% of isolates were susceptible to gentamicin and imipenem, respectively. These findings were consistent with broth dilution, where all strains were susceptible to gentamicin. Resistance was higher against polymyxin B and the fluoroquinolones. Silver sulfadiazine was effective invitro with a MIC ranging from 1 to 64μg/mL. As the MIC of silver sulfadiazine was lower than the concentration in a 1% preparation, such a product potentially represents a treatment option for dogs with P.aeruginosa otitis.

Identification and Characterization of Menadione and Benzethonium Chloride as Potential Treatments of Pierce's Disease of Grapevines.

Xylella fastidiosa infects a wide range of plant hosts and causes Pierce's disease (PD) of grapevines. The type 1 multidrug resistance (MDR) efflux system is essential for pathogenicity and survival of bacterial pathogens in planta. X. fastidiosa, with a single MDR system, is significantly more vulnerable to inhibition by small-molecule treatments than most bacterial pathogens that typically carry redundant MDR systems. A high-throughput cell viability assay using a green fluorescent protein-marked strain of X. fastidiosa Temecula 1 was developed to screen two Prestwick combinatorial small-molecule libraries of drugs and phytochemicals (1,600 chemicals in total) approved by the Food and Drug Administration and European Medicines Agency for cell growth inhibition. The screens revealed 215 chemicals that inhibited bacterial growth by >50% at 50 µM concentrations. Seven chemicals proved to lyse X. fastidiosa cells at 25 µM, including four phytochemicals. Menadione (2-methyl-1,4-naphthoquinone, vitamin K) from the phytochemical library and benzethonium chloride (a topical disinfectant) from the chemical library both showed significant bactericidal activity against X. fastidiosa. Both menadione and benzethonium chloride foliar spray (15 and 5 mM, respectively) and soil drench (5 and 25 mM, respectively) treatments were equally effective in reducing PD symptoms by 54 to 59% and revealed that the effects of both chemical treatments became systemic. However, menadione was phytotoxic when applied as a foliar spray at effective concentrations, causing significant loss of photosynthetic capacity.

Topical ophthalmic antimicrobials: unfulfilled demands and possibility of new investments in Brazil and in the United States

In general, topical ophthalmic drug products, especially those used for treating infections, present low effectiveness because of various reasons, from unfavorable drug physicochemical properties to physiological protective mechanisms of the eye. The fact is such group of products holds room for improvement, which could mean the development of better drugs or dosage forms. To achieve this, the knowledge of market composition is essential. The present work studied and compared the antimicrobial ophthalmic markets of Brazil and of the United States (US). Official databank of Brazilian Health Regulatory Agency and of US Food and Drug Administration were assessed for registered antimicrobial topical ophthalmic drug products. Brazilian market has registered greater number of drug products (119) than the US (94), but the latter involves more variety of substances and dosage forms. In both countries, non-innovative products registered as solutions of antibacterials, especially fluoroquinolones and aminoglycosides lead the market. Despite the clinical demand, the US has only one group of antimycotics (polyenes) registered, while in Brazil, there is not any ophthalmic antimycotic product marketed. This study evidences there is not only space for development of newer drugs and formulations but also a demand for already existing technologies and products in both countries.

Nano-silver modified porcine small intestinal submucosa for the treatment of infected partial-thickness burn wounds

Background and aimSilver has been widely used as a topical antimicrobial agent in burn wound care. In a previous study, we demonstrated the introduction of nano-silver particles to porcine small intestinal submucosa (NS-PSIS) led to significant enhancement in antibacterial property in repairing contaminated abdominal defect. In this study, we explored the efficacy of NS-PSIS in the treatment of Pseudomonas aeruginosa-infected partial-thickness burn wounds. Methods48 male Sprague-Dawley rats were divided into four groups of equal number. Standardized and reproducible Pseudomonas aeruginosa-infected partial-thickness thermal burns wound model were created using these rats. NS-PSIS, PSIS (porcine small intestinal submucosa) or lipido-colloid dressingss (Urgotul™) were tested for 14days to assess their ability to heal the rats’ burn wounds. Control group was without any treatment after the establishment of infected burn-wound. The wound contraction rate, animal body weight change, histological examination, and the quantification of IL-6 and C-reactive protein (CRP) were measured to evaluate the healing effects. ResultsNS-PSIS significantly promoted wound healing and recovered the normal growth of rats. There were significantly lower expression levels of pro-inflammatory cytokine (IL-6) and CRP in NS-PSIS group as compared with the PSIS or Urgotul group in the treatment of infected partial-thickness burn wounds. Histological exams revealed significant less inflammatory cells infiltrating, more re-epithelization and neovascularization in NS-PSIS group. There were also less inflammatory cells infiltrations in the major organs in NS-PSIS group. ConclusionsNano-silver modified porcine small intestinal submucosa (NS-PSIS) can be used as a biological derivative dressing for the treatment of infected partial-thickness burn wounds.

Optimising the short and long-term clinical outcomes for koalas (Phascolarctos cinereus) during treatment for chlamydial infection and disease.

Koalas (Phascolarctos cinereus) have suffered severe declines in the northern extent of their range due to a variety of threats, including habitat destruction, trauma from cars and dogs, climate change and importantly, disease. The most significant pathogen in koalas is Chlamydia pecorum, which causes inflammation and fibrosis at mucosal sites, resulting in blindness, infertility and death in severe cases. Chlamydia treatment can be problematic in koalas as the response to treatment is often poor in chronic cases and antimicrobial choice is limited. Thus, chlamydial disease is a severely threatening process for koala conservation. We investigated the short and long-term clinical outcomes for 167 koalas with Chlamydia that underwent capture, telemetric monitoring and intensive veterinary management as part of a large-scale population management program in South East Queensland. Chlamydia treatments included the standard regimen of daily subcutaneous chloramphenicol injections (60mg/kg) for 14 to 28-days, and a variety of non-standard regimens such as topical antimicrobials only (for ocular disease), surgical treatment only (for bilateral reproductive tract disease), and other antimicrobials/treatment lengths. To assess these regimens we analysed clinical records, field monitoring data and swab samples collected from the urogenital tract and ocular conjunctiva. Overall, in contrast to other studies, treatment was generally successful with 86.3% of treated koalas released back into the wild. The success of treatment rose to 94.8% however, when the standard treatment regimen was employed. Further, 100% of koalas that were also treated with surgical ovariohysterectomy (n = 12) remained healthy for a median of 466 days of post-treatment monitoring, demonstrating the benefits of surgical treatment. Previous studies reported 45-day chloramphenicol regimens, but the shorter standard regimen still achieved microbiological cure and reduces the risk of negative sequelae associated with treatment and/or captivity and treatment costs. Despite these positive clinical outcomes, alternatives to chloramphenicol are warranted due to its decreasing availability.

Wound Closure and Management.

The management of incisions and decisions on closure techniques for surgical wounds are driven by expected incisional morbidity and the severity of the potential morbidity for the patient. This article reviews current literature on the potential strategies to be considered in closing the skin and fascia of incisions. The review of the literature indicates that low-risk wounds for infection should be closed primarily with subcuticular suture, and adjunctive local measures should be avoided. Adjunctive measures of irrigation, topical antimicrobial agents, and negative pressure incisional therapy may have a role in high-risk wounds. Surgeons should strongly consider primary closure of contaminated wounds. The overall literature on adjuncts of wound irrigation, topical antimicrobials, and negative pressure wound therapy have potential to be of benefit but additional investigation is necessary since they do impact cost, patient experience, and antibiotic stewardship.

Enhanced topical delivery of non-complexed molecular iodine for Methicillin-resistant Staphylococcus aureus decolonization

Staphylococcus aureus, a leading cause of serious human infections in both healthcare and community settings, is increasingly difficult to control due to expanding resistance to multiple antibiotic classes. Methicillin-resistant S. aureus (MRSA) strains have disseminated on a global scale and are associated with adverse patient outcomes, increased hospital stays, and significant economic costs to the healthcare system. A proximal step in S. aureus infection is colonization of the nasal mucosa, and effective strategies to decolonize high risk patients to reduce the risk of invasive infection and nosocomial spread represent an important clinical priority. With rising resistance to mupirocin, the most common antibiotic utilized for nasal MRSA decontamination, we are examining the use of pure molecular iodine (I2)-based formulations for this indication. Recently, an iodophor formulation of povidone-iodine (PVP-I) has shown significant promise for nasal MRSA decontamination by swabbing the anterior nares of patients in hospital settings, but the I2 concentration in this treatment is less than 0.01% of total iodine species present and like all providone-iodine formulations causes skin staining. Here we determine that a novel non-staining formulation of I2 combined with the safe organic emollient glycerin delivers high local concentrations of the active antimicrobial entity (I2) with minimal evaporative loss, exhibits activity at ∼1 part per million against MRSA and other important Gram-positive and -negative human pathogens. This formulation for I2 topical delivery produced similar reductions in mean bacterial burden and was associated with fewer treatment failures (<2-logfold reduction) than PVP-I in a murine model of MRSA nasal decontamination. Formulations of I2 in glycerin emollient merit further exploration as topical disinfectants for human medical indications.

The downside of antimicrobial agents for wound healing.

The use of topical antimicrobials is beneficial for infection control in wound care because wound infection is the major cause of delayed healing. The advantages of topical over systemic antimicrobials include a higher concentration at the target site, fewer systemic adverse effects, and a lower incidence of antimicrobial resistance. Nowadays, topical antimicrobials are divided into three groups: disinfectants, antiseptics, and antibiotics. Only antiseptics and antibiotics can be applied to living skin; therefore, this review will focus only on these groups. The advantages of each topical antimicrobial are well established; however, their disadvantages remain prominent. It is widely known that antiseptics show higher cytotoxicity and a broader spectrum of activity than antibiotics, whereas antibiotics show a higher probability of bacterial resistance development. However, there are still many adverse effects, resulting from each topical antimicrobial. This review aims to summarize the possible adverse effects of commonly used antiseptics (biguanide, silver, iodine, chlorine compounds, and other antiseptics), antibiotics (bacitracin, mafenide, mupirocin, neomycin, and silver sulfadiazine), and natural antimicrobials (curcumin and honey). Moreover, the antimicrobials that should be avoided in particular populations are also summarized in this review in order to increase awareness for antimicrobial selection in those populations.