Treatment Of Local Infections Research Articles

Antibacterial and Anti-Inflammatory Activity of Branched Peptides Derived from Natural Host Defense Sequences.

Antibiotic resistance is a major global health threat, necessitating the development of new treatments and diverse molecules to combat severe infections and preserve the efficacy of existing drugs. Antimicrobial peptides (AMPs) offer a versatile arsenal against bacteria, and peptide structure branching can enhance their resistance to proteases and improve their overall efficacy. A small library of peptides derived from natural host defense peptides and synthesized in a tetrabranched form was selected against E. coli. Six selected branched peptides were further studied for antibacterial activity against a panel of strains, biofilm inhibition, protease resistance, and cytotoxicity. Their structure was predicted computationally and their mechanism of action was investigated by electron microscopy and by using fluorescent dyes. The peptide BAMP2 showed promise in a mouse skin infection model, indicating the potential for local infection treatment.

Melanin as a Photothermal Agent in Antimicrobial Systems.

Bacterial infection is one of the most problematic issues for human health and the resistance of bacteria to traditional antibiotics is a matter of huge concern. Therefore, research is focusing on the development of new strategies to efficiently kill these microorganisms. Recently, melanin is starting to be investigated for this purpose. Indeed, this very versatile material presents outstanding photothermal properties, already studied for photothermal therapy, which can be very useful for the light-induced eradication of bacteria. In this review, we present antibacterial melanin applications based on the photothermal effect, focusing both on the single action of melanin and on its combination with other antibacterial systems. Melanin, also thanks to its biocompatibility and ease of functionalization, has been demonstrated to be easily applicable as an antimicrobial agent, especially for the treatment of local infections.

Could light be a broad-spectrum antimicrobial?

A review on antimicrobial resistance mechanisms discussing the main light-based antimicrobial approaches including ultraviolet light (UV), antimicrobial photodynamic therapy (aPDT), and antimicrobial blue light (aBL). To describe antimicrobial resistance mechanisms and to present potential light-based alternatives to conventional antimicrobials. The paper was divided into different topics, starting with an approach to antimicrobial resistance mechanisms. Subsequently, emphasis was placed on innovative light-based antimicrobials approaches, including aBL, UV, and aPDT. The review suggests that blue light (400-470 nm) acts on endogenous porphyrins with peak absorption at 405 nm, thus not requiring the administration of photosensitizers, to trigger antimicrobial effects. In this regarding, the direct effect of aBL could be attributed to both the generation of reactive oxygen species (ROS), which induces microbicidal effects, and the inactivation of bacterial defense mechanisms. In turn, blue light combined with curcumin has been used in the treatment of dental infections. Otherwise, green light (495-570 nm) associated with the photosensitizer Rose Bengal has shown promising results both in wound closure due to the induction of additional collagen cross-link formation and in reducing the viability of Pseudomonas aeruginosa. Red light (620-750 nm) is the wavelength most commonly used in aPDT, presenting superior tissue penetration capability compared to blue and green light. Both red and infrared light act directly as photobiomodulation agents, promoting tissue repair with greater penetration depth for the infrared spectrum. Conversely, red light combined with methylene blue is the most commonly used technique in the treatment of localized infections. Meanwhile, infrared light associated with indocyanine green acts as a photothermal and photosensitizing agent, promoting thermal damage and production of ROS. Ultraviolet lights UVA, UVB, and UVC (200-400 nm) have antimicrobial potential related to inducing changes in DNA and generating both ROS and singlet oxygen. Furthermore, light can enhance the efficacy of traditional antimicrobial agents by deactivating microbial resistance, both through increasing the permeability of the cell membrane and by inhibiting the efflux pump and β-lactamases of the bacteria. The antimicrobial potential of light is extensive; however, there is a limitation regarding the depth of penetration of certain wavelengths into infected areas. Furthermore, there is a need for additional studies to determine the safety and efficacy of various approaches using light at its different wavelengths.

In vitro elution of amikacin, cefazolin, gentamicin, ampicillin/sulbactam, and meropenem from a commercially available calcium sulfate delivery kit.

The use of implantable antibiotic beads has become a frequent treatment modality for the management of surgical site infections in human and veterinary medicine. The objective of this study is to describe the elution kinetics of five antibiotics from a commercially available calcium sulfate antibiotic delivery kit. A secondary goal was to compare elution concentrations with minimal inhibitory concentrations (MIC) for commonly encountered bacteria from the University of Florida's veterinary microbiology laboratory database. Calcium sulfate powder was combined with amikacin, cefazolin, gentamicin, ampicillin/sulbactam, and meropenem. Triplicates of three antibiotic-loaded beads were immersed in 5 mL of phosphate-buffered saline (PBS) and kept at 37°C under constant agitation. Antibiotic-conditioned PBS was sampled at 14 time points from 1-h to 30 days and analyzed by liquid chromatography to determine the antibiotic concentration. All beads eluted concentrations of antibiotics for the 30-day sampling period, except for ampicillin/sulbactam, with the most antibiotics being eluted within the first week. The concentration of antibiotics within the eluent within the first 3-9 days (3- and 5-mm beads, respectively) was greater than the MIC of common isolates. The 5 mm bead samples were superior in maintaining higher concentrations for a longer period, compared to the 3-mm beads. CSH beads eluted antibiotics over the 30-day course of the study. Most of the antibiotic elution occurred within the first week and was maintained above the MIC of commonly encountered isolates. This information may be useful for clinical decision making for treatment of local infections encountered in practice.

Poly Lactic-co-Glycolic Acid (PLGA) Loaded with a Squaraine Dye as Photosensitizer for Antimicrobial Photodynamic Therapy.

Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections.

NIR dye-based electrospun fibers for antimicrobial photodynamic therapy

AbstractAntimicrobial photodynamic therapy (aPDT) has emerged as a promising strategy to improve antimicrobial treatment and face the antibiotic resistance to conventional therapy. Among the different photosensitizers, Near Infrared (NIR) polymethine dyes (Squaraines, SQs and Cyanines, CYs) have attracted considerable attention although, their poor aqueous solubility and stability still limit their application. Their incorporation inside nanoparticles (NPs) or into electrospun fibers, could help to prevent dye aggregation, protect their photochemical properties, and play a key role in the infection treatment.Cys and SQs were characterized before and after the incorporation, showing improved optical properties and photostability. In addition, their ability to produce Reactive Oxygen Species (ROS), responsible of bacterial death, was evaluated, proving that the ROS generation ability is preserved after the incorporation. Furthermore, in vitro antimicrobial studies against Gram-negative and Gram-positive models showed a good antimicrobial effect after the irradiation, confirming the potential of these nanophotosensitizers for aPDT in the local treatment of infections.

Thermosensitive gel of pomegranate peel extract as alternative for the treatment of local infections

Thermosensitive gel of pomegranate peel extract as alternative for the treatment of local infections

Systemic application of bone-targeting peptidoglycan hydrolases as a novel treatment approach for staphylococcal bone infection.

The rising prevalence of antimicrobial resistance in S. aureus has rendered treatment of staphylococcal infections increasingly difficult, making the discovery of alternative treatment options a high priority. Peptidoglycan hydrolases, a diverse group of bacteriolytic enzymes, show high promise as such alternatives due to their rapid and specific lysis of bacterial cells, independent of antibiotic resistance profiles. However, using these enzymes for the systemic treatment of local infections, such as osteomyelitis foci, needs improvement, as the therapeutic distributes throughout the whole host, resulting in low concentrations at the actual infection site. In addition, the occurrence of intracellularly persisting bacteria can lead to relapsing infections. Here, we describe an approach using tissue-targeting to increase the local concentration of therapeutic enzymes in the infected bone. The enzymes were modified with a short targeting moiety that mediated accumulation of the therapeutic in osteoblasts and additionally enables targeting of intracellularly surviving bacteria.

Hyaluronic Acid-Alginate Homogeneous Structures with Polylactide Coating Applied in Controlled Antibiotic Release.

The use of a controlled-release drug carrier is an innovative solution for the treatment of local infections, in particular in dentistry, skin diseases, and in open wounds. The biocompatibility, biodegradability, the possibility of a large amount of drug adsorbed (especially those with hydrophilic properties), and the ability to create structures of any shape and size are the reasons for hydrogels to be frequently studied. The main disadvantage of hydrogel carriers is the rapid rate of drug release; hence, in this study, an attempt was made to additionally chemically cross-link 1-ethyl-3-(3-dimethyl aminopropyl)-1-carbodiimide hydrochloride (EDC) with the hyaluronic acid-alginate (HA-SAL) structure. The answer to significantly reduce the mass flux typical for hydrogel structure was to surround it with a polymer layer using a dry cover. By coating the carriers with polylactide, the release time was increased by around forty times. As the carriers were designed to reduce local bacterial infections, among others in dentistry, the released antibiotics were amoxycillin, metronidazole, and doxycycline.

Sprayable Antibacterial Hydrogels by Simply Mixing of Aminoglycoside Antibiotics and Cellulose Nanocrystals for the Treatment of Infected Wounds.

Antibiotic hydrogels with sustained release profiles are recognized as promising candidates to treat local bacterial infections with reduced adverse effects. However, it still remains challenging for clinical translation of these antibiotic gels due to safety concern of gel ingredients, complicated synthesis and fabrication procedures, and unsatisfactory rheological properties for practical uses in vivo. Herein, the preparation of a type of sprayable hydrogels by ionic interactions between aminoglycosides and cellulose nanocrystals (CNC) is proposed for the treatment of local infections such as bacteria-infected wounds. The CNC-based hydrogels are applicable for all kinds of aminoglycoside antibiotics and show excellent gel stability and rheological behaviors such as shear thinning and fast self-healing, allowing facile administration by injection or spraying. The hydrogels exhibit efficient antibacterial activity both in vitro and in vivo, and accelerate bacteria-infected wounds by spraying on the infected area. The proposed hydrogels by simply mixing of aminoglycosides and CNC provide great prospects for clinical translation in the treatment of local infections.

Rifampicin-loaded PLGA nanoparticles for local treatment of musculoskeletal infections: Formulation and characterization

Systemic treatment of orthopedic device-related infections requires potentially toxic doses to reach local therapeutic levels. A locally applied nanosized drug delivery system can provide a high drug dose at the target site. Branched PLGA of lower molar mass was used for rifampicin-loaded nanoparticles (RIF-NPs) formulation by the nanoprecipitation method. The formulation variables influenced the NPs size ranging from 200 to 380 nm. The missing peak of crystalline rifampicin on the DSC scan of the NPs indicates that the drug was molecularly dispersed. The negative charge of the NPs in the physiological buffer was masked by a nonionic surfactant or converted to a positive one by a cationic surfactant, which promotes bioadhesion, penetration, and antimicrobial effect of locally applied RIF-NPs without being toxic to proliferation. Low values of loading capacity showed that PLGA predominates in the NPs, which, however, perform their function as a drug carrier ensuring sustained RIF release. The ex vivo dissolution study of RIF-NPs impregnated into the cancellous allogeneic bone grafts showed a low initial burst followed by sustained release of RIF for 7 days. Rifampicin-loaded PLGA nanoparticles may contribute to the prevention of resistant biofilm formation in patients with implanted devices and the local treatment of infections in open musculoskeletal injuries.

Study of Compound Sanqi Nanoparticles for Local Infection of Hydrocephalus Patients after Neurosurgery Medium Craniocerebral Injury.

Panax notoginseng is the dried root and rhizome of Panax notoginseng, which has the effect of lowering blood lipid, lowering blood pressure and promoting blood circulation to remove blood stasis. At present, the research on Panax notoginseng is mainly focused on its pharmacological action and its compound preparation, but the research on the granule of Panax notoginseng is less. This paper mainly studied the clinical study of compound notoginseng nanoparticles in the treatment of local infection in patients with hydrocephalus after medium craniocerebral injury in neurosurgery. The purpose of this article is to investigate the effects of compound notoginseng nanoparticles on serum TNF-α, IL-2 and IL-6 in rats with craniocerebral injury and to verify the protective effect of compound notoginseng nanoparticles on the body after craniocerebral injury. In this paper, 90 patients admitted to a hospital in this city were divided into a control group, model group and compound notoginseng nanoparticle group. According to the Zealonga method, the neurological function deficit score of experimental rats in each group was evaluated. The levels of TNF-α, IL-2 and IL-6 in the serum of the three groups were observed 1, 3 and 5 days after treatment. RESULTS: Compared with serum TNF-α, IL-2 and IL-6 of the three groups, there were significant differences in the main effects of time and intervention (P < 0.05). CONCLUSIONS: Compound notoginseng nanoparticles can reduce the contents of TNF-α and IL-6 in serum and increase the expression of IL-2 in rats with craniocerebral injury.

Evaluating Tannins and Flavonoids from Traditionally Used Medicinal Plants with Biofilm Inhibitory Effects against MRGN E. coli.

In the search for alternative treatment options for infections with multi-resistant germs, traditionally used medicinal plants are currently being examined more intensively. In this study, the antimicrobial and anti-biofilm activities of 14 herbal drugs were investigated. Nine of the tested drugs were traditionally used in Europe for treatment of local infections. For comparison, another five drugs monographed in the European Pharmacopoeia were used. Additionally, the total tannin and flavonoid contents of all tested drugs were analyzed. HPLC fingerprints were recorded to obtain further insights into the components of the extracts. The aim of the study was to identify herbal drugs that might be useable for treatment of infectious diseases, even with multidrug resistant E. coli, and to correlate the antimicrobial activity with the total content of tannins and flavonoids. The agar diffusion test and anti-biofilm assay were used to evaluate the antimicrobial potential of different extracts from the plants. Colorimetric methods (from European Pharmacopeia) were used for determination of total tannins and flavonoids. The direct antimicrobial activity of most of the tested extracts was low to moderate. The anti-biofilm activity was found to be down to 10 µg mL−1 for some extracts. Tannin contents between 2.2% and 10.4% of dry weight and total flavonoid contents between 0.1% and 1.6% were found. Correlation analysis indicates that the antimicrobial and the anti-biofilm activity is significantly (p < 0.05) dependent on tannin content, but not on flavonoid content. The data analysis revealed that tannin-rich herbal drugs inhibit pathogens in different ways. Thus, some of the tested herbal drugs might be useable for local infections with multi-resistant biofilm-forming pathogens. For some of the tested drugs, this is the first report about anti-biofilm activity, as well as total tannin and flavonoid content.

RW-BP100-4D, a Promising Antimicrobial Candidate With Broad-Spectrum Bactericidal Activity.

With the rapid emergence and dissemination of antimicrobial resistance (AMR) genes in bacteria from animal, animal-derived food and human clinic, it is of great significance to develop new approaches to combat the multidrug-resistant bacteria. This study presented a short linear antimicrobial peptide RW-BP100-4D, which was derived from RW-BP100 (RRLFRRILRWL-NH2) by transforming the N-terminal 4th amino acid from L- to D-enantiomer. This modification remarkably reduced the peptide cytotoxicity to mammalian cells, as indicated by hemolytic and cytotoxicity assays. Meanwhile, the antimicrobial activity of RW-BP100-4D was improved against a more variety of Gram-positive and Gram-negative bacteria (sensitive and resistant) as well as fungi. Also, RW-BP100-4D showed strong in vitro anti-biofilm activity in a concentration-dependent manner, including inhibition of the biofilm-formation and dispersion of the mature biofilms of Staphylococcus aureus. RW-BP100-4D could be efficiently uptaken by bovine mammary epithelial cells (MAC-T) cells to eliminate the intracellular S. aureus ATCC29213 and Salmonella enterica ATCC13076. Moreover, RW-BP100-4D was highly effective in food disinfection of multiple bacterial contamination (including S. aureus, Listeria monocytogenesis, Escherichia coli O157: H7, Campylobacter jejuni, S. enterica, and Shewanella putrefaction, 3.61 ± 0.063 log reduction) on chicken meat, and could kill 99.99% of the methicillin-resistant Staphylococcus aureus (MRSA) strain in the mouse skin infection model. In summary, RW-BP100-4D is a promising antimicrobial candidate for application on food disinfection and local infection treatment. However, the protease-sensitivity of RW-BP100-4D and toxic effect at higher doses reduced the therapeutic effect of the candidate peptide in vivo and should be improved in the future studies.

Aplicação dos óleos ozonizados nos sistemas do corpo humano e cavidade oral

ABSTRACT Wound healing consists of the coordinated cascade of molecular, cellular and biochemical events that interact for tissue recomposition to occur. The interruption or failure in this process can trigger the delay in closing the lesion and chronic wounds, in addition to infections. Ozonotherapy proves to be a promising alternative, capable of assisting in the tissue healing process, modulating the inflammatory response and preventing the development of infection. To present, analyze and discuss, through a literature review, the use of Ozonated Oils in the repair of the human body and oral cavity systems. SciELO, LILACS, MEDLINE and PubMed databases were consulted, using the following DeCS / MeSH descriptors: “ozonized oil”; “healing”; “ozone therapy”. After crossing, counting and analyzing, 13 studies were selected, according to the theme. Due to the complementary theoretical foundation, 44 articles were included, totaling 57 articles used for the present review. Ozonized Oil therapy has beneficial clinical effects, which include antimicrobial, immunostimulating, analgesic, antipoxic, immunoregulatory and antioxidant action. Topical management of ozone has proven effective for the treatment of foot-and-mouth disease, gingivitis, ulcers and dermatitis, contributing to pain relief and healing. Infectious skin diseases, abscesses, allergic skin diseases, scaly erythema, psoriasis and palmoplantar pustulosis are pathological conditions, the treatment of which benefits from the application of Ozonized Oils. Ozonized Oils have been shown to be effective in the treatment of local infections, when in appropriate formulations and in controlled cases, being a promising therapeutic alternative for tissue repair.

14. Effects of an Opt-Out Protocol for Antibiotic De-escalation among Selected Patients with Suspected Sepsis: The DETOURS Trial

BackgroundSepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. We conducted a randomized controlled trial (NCT03517007) of an opt-out protocol to decrease unnecessary antibiotics in selected patients with suspected sepsis.MethodsWe evaluated non-ICU adults remaining on broad-spectrum antibiotics with negative blood cultures at 48-96 hours at ten U.S. hospitals during September 2018-May 2020. A 23-item safety check excluded patients with ongoing signs of infection, concerning or inadequate microbiologic data, or high-risk conditions (Figure 1). Eligible patients were randomized to the opt-out protocol vs. usual care. The primary outcome was 30-day post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted by a pharmacist or physician to encourage antibiotic discontinuation or de-escalation using opt-out language, discuss rationale for continuing antibiotics, working diagnosis, and de-escalation and duration plans. Hurdle models separately compared the odds of antibiotic continuation and DOT distributions among those who continued antibiotics.Components of the De-Escalating Empiric Therapy: Opting-OUt of Rx in Selected patients with Suspected Sepsis (DETOURS) Trial Protocol ResultsAmong 9606 screened, 767 (8%) were enrolled (Figure 2). Common reasons for exclusion were antibiotics given prior to blood culture (35%), positive culture from non-blood sites (26%), and increased oxygen requirement (21%). Intervention patients had 32% lower odds of antibiotic continuation (79% vs. 84%, OR 0.68, 95% confidence interval [0.47, 0.98]). DOT distributions among those who continued antibiotics were similar (ratio of means 1.06 [0.88-1.26], Figure 3). Fewer intervention patients were exposed to extended-spectrum agents (38% vs. 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was not safe (31%). Safety outcomes such as mortality, readmission, sepsis relapse, C. difficile, and length of stay did not differ.DETOURS Trial Flow Diagram Flow of participants through the DETOURS Trial.Observed Days of Antibiotic Therapy Among Intervention and Control Subjects in the DETOURS Trial Post-enrollment days of antibiotic therapy among 767 DETOURS Trial participants in 10 US acute care hospitals within 30 days after enrollment. Dark pink color indicates percent overlap between intervention (purple) and control (light pink) groups.ConclusionIn this patient-level randomized trial of a stewardship intervention, the opt-out de-escalation protocol targeting selected patients with suspected sepsis resulted in more antibiotic discontinuations but did not affect safety events.Disclosures Rebekah W. Moehring, MD, MPH, UpToDate, Inc. (Other Financial or Material Support, Author Royalties) Michael Z. David, MD PhD, GSK (Board Member) Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)

Nanoparticle-Hydrogel Systems Containing Platensimycin for Local Treatment of Methicillin-Resistant Staphylococcus aureus Infection.

Skin and soft tissue infections require effective and sustained topical administration. Platensimycin (PTM) is a natural drug lead that targets bacterial fatty acid synthases and has a great potential to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the use of PTM against local MRSA infections, we prepared polyacrylamide hydrogels containing polyamidoamine (PAMAM)/PTM nanoparticles (NP-gel(PTM)) for the controlled release of PTM. NP-gel(PTM) can continuously inhibit the growth of MRSA and its biofilm formation in simulated drug flow models in vitro. In situ implantation of NP-gel(PTM) could treat MRSA-infected subcutaneous soft tissues without toxicity. For MRSA-infected skin wounds, NP-gel(PTM) not only showed strong anti-MRSA activity but also accelerated more wound healing than the widely used antibiotic mupirocin. Collectively, PTM is expected to be used in this safe and effective NP-gel delivery platform for the treatment of local infections, which might help to alleviate the current antibiotic resistance crisis.

Antibacterial directed chemotherapy using AS-48 peptide immobilized on biomimetic magnetic nanoparticles combined with magnetic hyperthermia

The design of new strategies to increase the effectiveness of the antibacterial treatments is a main goal in public health. So, the aim of the study was to achieve a local antibacterial directed therapy as novel alternative allowing both, the delivery of the drug at the target, while minimizing undesirable side effects, thus anticipating an enhanced effectiveness. Hence, we have developed an innovative nanoformulation composed by biomimetic magnetic nanoparticles functionalized with the antimicrobial peptide AS-48 and its potential against Gram-positive and Gram-negative bacteria, either by itself or combined with magnetic hyperthermia has been investigated. Besides, the physical properties, binding efficiency, stability and mechanism of action of this nanoassembly are analyzed. Remarkably, the nanoassembly has a strong bactericidal effect on Gram-positive bacteria, but surprisingly also on E. coli and, finally, when combined with magnetic hyperthermia, on P. aeruginosa and K. pneumoniae. The results obtained represent a breakthrough since it allows a local treatment of infections, reducing and concentrating the dose of antimicrobial compounds, avoiding secondary effects, including the resistance generation and particularly because the combination with magnetic hyperthermia helps sensitizing resistant bacteria to the bactericidal effect of AS-48. Thus, this new formulation should be considered a promising tool in the antibacterial fight.

Optimización de variables en ensayos de actividad antifúngica fotodinámica frente a especies de Candida

Oral infections due to yeasts of the genus Candida are very common in patients with predisposing factors, such as physiological conditions or certain underlying diseases. Moreover, oral candidiasis can also evolve into disseminated forms. In this work, strains of the genus Candida were studied to establish the optimal radiation conditions for photosensitizing compounds, in a photodynamic antifungal therapy protocol. A total of 39 isolates were evaluated. The strains were exposed to twelve dyestuffs, eight radiation sources and three different exposure times. Orthotoluidine blue exhibited good photodynamic activity, in combination with exposure to a 20W reflector lamp LED (light-emitting diode) light for 60minutes. When considering the difficulties of using conventional antifungal drugs, the emergence of resistant strains, recurrences, and adverse reactions of certain commonly used drugs, the photodynamic antifungal therapy is a promising strategy for the treatment of localized infections.

Laser Photobiomodulation and Antimicrobial Photodynamic Therapy in the Treatment of Ovine Otitis

Background: Otitis is a severe inflammation of the skin of the auditory canal which can impact animals of all ages. In sheep, this disease can occur in isolated cases or in the entire flock. Laser photobiomodulation can be used in combination with medication or as single therapy and the effects are analgesia, modulation of the inflammatory process, edema reduction, tissue restoration and stimulation of local microcirculation. Antimicrobial photodynamic therapy stands out as a promising alternative to antimicrobial drugs for the treatment of localized infections. This study aimed to report the use of laser phototherapies on a sheep with bacterial otitis.Case: A case of bacterial otitis in a 4-year-old sheep, Dorper, was treated at the Veterinary Hospital of the State University of Santa Cruz. In the anamnesis, the owner reported that the patient presented crusts in the auricular pavilions, and had been medicated with oxytetracycline 20%, administered intramuscularly, for two days and the crusts cleaned with iodine 10%, but the animal did not present clinical improvement. On physical examination, the animal presented constant head swaying, edema of the ears, otalgia, enlarged parotid lymph nodes and ear wounds. No ear discharge was observed, and the initial diagnosis was aural hematoma. The treatment prescribed was laser photobiomodulation for three consecutive days. The lesions were irradiated with a diode laser with a power of 0.1 W, irradiance of 3.5 W/cm2, continuous emission, spot area of 0.028 cm2, wavelength of 808 nm, energy of 4J/point, and fluency/point of 142.8J/cm2, with seven points on the external surface and four points on the internal surface of both ears. Two points were also targeted on the parotid lymph nodes with infrared laser (λ = 808 nm), with energy of 2J/point. On the fourth day of hospitalization, there was a reduction in lesions, decreased edema and absence of pain and on the sixth day of hospitalization, the patient presented mucopurulent otorrhea. The material from the auricular pavilions was collected for cytological examination, confirming the clinical diagnosis of bacterial otitis. Two sessions of Antimicrobial Photodynamic Therapy (aPDT) were performed with an interval of 48 hours, with application of 0.01 % methylene blue, pre-irradiation time of five minutes and irradiation with diode laser with a power of 0.1 W, 660 nm wavelength and 9J/point energy. On the 10 th day after the start of the treatment, there was no pain, healing of ear wounds, and no otorrhea. An additional photobiomodulation session was performed on the unhealed wounds in the auditory canal with red laser (λ = 660nm), on 5 points with an energy of 1J/point. On the 15th day, the left ear was healed and the right ear presented otorrhea, and a further session of aPDT was performed. On the 17th day after starting treatment there was no secretion and all lesions were healed. The patient was subsequently monitored for one month, showing no change or relapse.Discussion: Laser photobiomodulation treatment and antimicrobial photodynamic therapy were efficient in treating bacterial otitis without the use of antibiotics, promoting clinical improvement and patient well-being, making it an alternative to conventional treatment. After searches on the Pubmed, Scielo and Escopus databases using photobiomodulation and antimicrobial photodynamic therapy in sheep otitis as descriptors, this is believed to be the first report on the use of laser phototherapy in sheep otitis. Further studies are needed to establish the dosimetry and frequency of the sessions, as, besides considering animal well-being, this species is an excellent model for human experimentation.